scholarly journals Protein motions and dynamic effects in enzyme catalysis

2015 ◽  
Vol 17 (46) ◽  
pp. 30817-30827 ◽  
Author(s):  
Louis Y. P. Luk ◽  
E. Joel Loveridge ◽  
Rudolf K. Allemann
Keyword(s):  
Dihydrofolate Reductase ◽  
Enzyme Catalysis ◽  
Catalytic Cycle ◽  
Dynamic Effects ◽  
Dynamic Coupling ◽  
Protein Motions ◽  
Catalytic Power

While the full catalytic power of dihydrofolate reductase depends on finely tuning protein motions in each step of the catalytic cycle, dynamic coupling to the actual chemical step is detrimental to catalysis.

Conformational changes in the catalytic cycle of protochlorophyllide oxidoreductase: what lessons can be learnt from dihydrofolate reductase?

2009 ◽  
Vol 37 (2) ◽  
pp. 354-357 ◽  
Author(s):  
Derren J. Heyes ◽  
Nigel S. Scrutton
Keyword(s):  
Dihydrofolate Reductase ◽  
Conformational Changes ◽  
Catalytic Mechanism ◽  
Structural Information ◽  
Chlorophyll Biosynthesis ◽  
Catalytic Cycle ◽  
Protochlorophyllide Oxidoreductase ◽  
Protein Motions ◽  
Kinetic Information ◽  
Related Enzyme

In chlorophyll biosynthesis, the light-activated enzyme, POR (protochlorophyllide oxidoreductase), has been shown to be an excellent model system for studying the role of protein motions during catalysis. The catalytic cycle of POR is understood in detail and comprises an initial photochemical reaction, which is followed by a number of ‘dark’ steps. The latter steps in the reaction cycle have been shown to involve a series of ordered product release and substrate rebinding events and are known to require conformational changes in the protein in order to proceed. However, owing to the current lack of any structural information on the enzyme, the nature of these conformational rearrangements remains poorly understood. By contrast, there is a wealth of structural and kinetic information available on the closely related enzyme dihydrofolate reductase, which is known to have a similar catalytic mechanism to POR. Dihydrofolate reductase is able to adopt an ‘occluded’ and a ‘closed’ structure, depending on which ligand is bound in the active site, and as a result, the catalytic cycle is controlled by a ‘switching’ between these two conformations. By analogy, we suggest that a similar cycling between different conformations may be operating in POR.

scholarly journals Minimization of dynamic effects in the evolution of dihydrofolate reductase

2016 ◽  
Vol 7 (5) ◽  
pp. 3248-3255 ◽  
Author(s):  
J. Javier Ruiz-Pernía ◽  
Enas Behiry ◽  
Louis Y. P. Luk ◽  
E. Joel Loveridge ◽  
Iñaki Tuñón ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Enzyme Catalysis ◽  
Isotope Labeling ◽  
Conformational Dynamics ◽  
Dynamic Effects ◽  
Powerful Technique ◽  
P Protein

Protein isotope labeling is a powerful technique to probe functionally important motions in enzyme catalysis and can be applied to investigate the conformational dynamics of proteins.

Dihydrofolate Reductase as a Model for Enzyme Catalysis

2015 ◽  
Vol 4 (2) ◽  
pp. 77-86 ◽  
Author(s):  
Kevin Francis ◽  
Amnon Kohen
Keyword(s):  
Dihydrofolate Reductase ◽  
Enzyme Catalysis

scholarly journals Site-Specific Tryptophan Labels Reveal Local Microsecond–Millisecond Motions of Dihydrofolate Reductase

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3819
Author(s):  
Morgan B. Vaughn ◽  
Chloe Biren ◽  
Qun Li ◽  
Ashwin Ragupathi ◽  
R. Brian Dyer
Keyword(s):  
Dihydrofolate Reductase ◽  
Conformational Changes ◽  
Collective Motion ◽  
Tryptophan Fluorescence ◽  
Slow Phase ◽  
Enzyme Dynamics ◽  
Wild Type ◽  
Two Phase ◽  
Protein Motions ◽  
The Individual

Many enzymes are known to change conformations during their catalytic cycle, but the role of these protein motions is not well understood. Escherichia coli dihydrofolate reductase (DHFR) is a small, flexible enzyme that is often used as a model system for understanding enzyme dynamics. Recently, native tryptophan fluorescence was used as a probe to study micro- to millisecond dynamics of DHFR. Yet, because DHFR has five native tryptophans, the origin of the observed conformational changes could not be assigned to a specific region within the enzyme. Here, we use DHFR mutants, each with a single tryptophan as a probe for temperature jump fluorescence spectroscopy, to further inform our understanding of DHFR dynamics. The equilibrium tryptophan fluorescence of the mutants shows that each tryptophan is in a different environment and that wild-type DHFR fluorescence is not a simple summation of all the individual tryptophan fluorescence signatures due to tryptophan–tryptophan interactions. Additionally, each mutant exhibits a two-phase relaxation profile corresponding to ligand association/dissociation convolved with associated conformational changes and a slow conformational change that is independent of ligand association and dissociation, similar to the wild-type enzyme. However, the relaxation rate of the slow phase depends on the location of the tryptophan within the enzyme, supporting the conclusion that the individual tryptophan fluorescence dynamics do not originate from a single collective motion, but instead report on local motions throughout the enzyme.

Kelvin-Helmholtz waves in the ocean?

1977 ◽  
Vol 82 (1) ◽  
pp. 1-16 ◽  
Author(s):  
J. J. Mahony
Keyword(s):  
Gravity Waves ◽  
Stability Boundary ◽  
Pressure Fluctuations ◽  
Dynamic Effects ◽  
Dynamic Coupling ◽  
Transfer Rates ◽  
Turbulent Pressure ◽  
The Mean ◽  
The Stability ◽  
Energy And Momentum

Large amplitude short waves confined near the crests of a swell have been observed when a stiff breeze was blowing against the swell. This would seem to imply the existence of both a wavelength-selective generating mechanism and a trapping mechanism, neither of which is to be expected of surface gravity waves of the observed length. It is suggested that there are significant changes in the dynamics of such waves if allowance is made for the dynamic coupling between wind and waves. For a Kelvin-Helmholtz model it is shown that energy transfer rates from the turbulent pressure fluctuations are greatly enhanced for subcritical conditions by the inclusion of the dynamic coupling. The group velocity of subcritical waves is profoundly affected, becoming infinite at the stability boundary. Thus subcritical waves could be trapped on a swell. An examination of the effects of wind shear suggest that Kelvin-Helmholtz type instability could still be present, although for stronger winds, particularly for rather longer waves.The energy and momentum fed from the mean wind, being trapped at crests of the swell, may contribute significantly to the attenuation of the swell. The profound wave dynamic effects of the coupling between the wind and the swell for short gravity waves may be of significance in other oceanic phenomena, even when the Kelvin-Helmholtz type of instability is not present.

Functional role for Tyr 31 in the catalytic cycle of chicken dihydrofolate reductase

2003 ◽  
Vol 51 (2) ◽  
pp. 216-223 ◽  
Author(s):  
Paul Shrimpton ◽  
Alex Mullaney ◽  
Rudolf K. Allemann
Keyword(s):  
Dihydrofolate Reductase ◽  
Functional Role ◽  
Catalytic Cycle
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