Toolkit/DHFR/LOV2 fusion

DHFR/LOV2 fusion

Multi-Component Switch·Research·Since 2024

Also known as: engineered photoswitch, light-regulated Dihydrofolate Reductase (DHFR) enzyme

Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.

Summary

The DHFR/LOV2 fusion is an engineered photoswitch in which the LOV2 light-sensing module was used to create a light-regulated dihydrofolate reductase (DHFR) enzyme. Source evidence indicates that light activation modulates DHFR catalysis through allosteric effects associated with local disorder and altered transition-state thermodynamics.

Usefulness & Problems

Why this is useful

This tool is useful for studying how light-responsive allostery can be coupled to enzyme catalysis in a defined fusion protein. The available evidence specifically supports its value as a model system for dissecting relationships among photosensory input, local disorder, thermal stability, and catalytic output.

Problem solved

It addresses the problem of engineering an enzyme whose catalytic behavior can be regulated by light through an appended sensory domain. The cited work also uses this system to probe how allosteric tuning mutations reshape the tradeoff between activity and stability.

Problem links

Need conditional recombination or state switching

Derived

The DHFR/LOV2 fusion is an engineered photoswitch in which the LOV2 light-sensing module was used to create a light-regulated dihydrofolate reductase (DHFR) enzyme. Source evidence supports that light activation alters DHFR catalysis through allosteric effects linked to local disorder and changes in transition-state thermodynamics.

Need precise spatiotemporal control with light input

Derived

The DHFR/LOV2 fusion is an engineered photoswitch in which the LOV2 light-sensing module was used to create a light-regulated dihydrofolate reductase (DHFR) enzyme. Source evidence supports that light activation alters DHFR catalysis through allosteric effects linked to local disorder and changes in transition-state thermodynamics.

Taxonomy & Function

Implementation Constraints

cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: multi component delivery burdenimplementation constraint: spectral hardware requirementoperating role: actuatoroperating role: sensorswitch architecture: multi componentswitch architecture: uncaging

The construct is described as a fusion in which LOV2 was used to create a light-regulated DHFR enzyme, supporting domain-fusion-based implementation. The provided evidence does not report expression system, chromophore requirements, linker design, or delivery considerations.

Evidence is currently limited to a single cited 2024 study and a small set of mechanistic claims. The supplied evidence does not specify quantitative performance metrics, illumination wavelengths, host organism, construct architecture, or validation in applications beyond the engineered enzyme context.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 2correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 3correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 4correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 5correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 6correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 7correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 8correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 9correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 10correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 11correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 12correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 13correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 14correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 15correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 16correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 17correlationsupports2024Source 1needs review

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.
Claim 18mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 19mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 20mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 21mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 22mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 23mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 24mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 25mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 26mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 27mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 28mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 29mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 30mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 31mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 32mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 33mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 34mechanistic associationsupports2024Source 1needs review

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch
Claim 35mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 36mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 37mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 38mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 39mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 40mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 41mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 42mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 43mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 44mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 45mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 46mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 47mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 48mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 49mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 50mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 51mechanistic modelsupports2024Source 1needs review

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.
Claim 52mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 53mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 54mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 55mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 56mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 57mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 58mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 59mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 60mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 61mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 62mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 63mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 64mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 65mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 66mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 67mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 68mutation effectsupports2024Source 1needs review

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.
Claim 69photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 70photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 71photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 72photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 73photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 74photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 75photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 76photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 77photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 78photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 79photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 80photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 81photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 82photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 83photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 84photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 85photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.
Claim 86photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 87photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 88photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 89photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 90photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 91photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 92photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 93photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 94photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 95photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 96photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 97photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 98photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 99photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 100photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 101photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 102photoactivation effectsupports2024Source 1needs review

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion
Claim 103stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 104stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 105stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 106stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 107stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 108stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 109stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 110stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 111stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 112stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 113stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 114stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 115stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 116stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 117stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 118stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.
Claim 119stability propertysupports2024Source 1needs review

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.

Approval Evidence

1 source7 linked approval claimsfirst-pass slug dhfr-lov2-fusion
we used LOV2 to create a light-regulated Dihydrofolate Reductase (DHFR) enzyme

Source:

correlationsupports

Many allostery-tuning mutations showed a negative correlation between light-induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Many of the allostery tuning mutations showed a negative correlation between the light induced change in thermal stability and catalytic activity, suggesting an activity-stability tradeoff.

Source:

mechanistic associationsupports

Local disorder is associated with enhanced catalysis in the engineered photoswitch.

Local disorder is associated with enhanced catalysis in an engineered photoswitch

Source:

mechanistic modelsupports

The energetic effect of light activation on transition state free energy was composed of a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

The energetic effect of light activation on the transition state free energy was composed of two opposing forces: a favorable reduction in the enthalpic transition state barrier offset by an entropic penalty.

Source:

mutation effectsupports

Allostery-tuning mutations in DHFR modulated the enthalpy-entropy tradeoff by either accentuating the enthalpic benefit or minimizing the entropic penalty, but not both.

Allostery-tuning mutations in DHFR acted through this tradeoff, either accentuating the enthalpic benefit or minimizing the entropic penalty but never improving both.

Source:

photoactivation effectsupports

LOV2 photoactivation lowered the catalytic transition free energy of the lit state relative to the dark state in the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (2) lowered the catalytic transition free energy of the lit state relative to the dark state.

Source:

photoactivation effectsupports

LOV2 photoactivation thermally destabilized the DHFR/LOV2 fusion.

LOV2 photoactivation simultaneously: (1) thermally destabilized the fusion

Source:

stability propertysupports

The DHFR/LOV2 fusion was marginally stable at physiological temperatures.

We found that the DHFR/LOV2 fusion was marginally stable at physiological temperatures.

Source:

Comparisons

Source-backed strengths

The source literature supports that the fusion produces a light-regulated DHFR and provides mechanistic analysis linking enhanced catalysis to local disorder. It also reports a mechanistic model in which light lowers the enthalpic transition-state barrier while incurring an entropic penalty, and notes a negative correlation between light-induced thermal stability changes and catalytic activity across many allostery-tuning mutations.

DHFR/LOV2 fusion and engineered focal adhesion kinase two-input gate address a similar problem space because they share recombination.

Shared frame: same top-level item type; shared target processes: recombination; shared mechanisms: allosteric switching; same primary input modality: light

Compared with OptoORAI1

DHFR/LOV2 fusion and OptoORAI1 address a similar problem space because they share recombination.

Shared frame: same top-level item type; shared target processes: recombination; shared mechanisms: allosteric switching; same primary input modality: light

DHFR/LOV2 fusion and photoactivatable diaphanous autoregulatory domain address a similar problem space because they share recombination.

Shared frame: same top-level item type; shared target processes: recombination; shared mechanisms: allosteric switching; same primary input modality: light

Ranked Citations

  1. 1.

    Extracted from this source document.