Intrinsic motions along an enzymatic reaction trajectory

@article{HenzlerWildman2007IntrinsicMA,
  title={Intrinsic motions along an enzymatic reaction trajectory},
  author={Katherine A. Henzler-Wildman and Vu Hong Thai and Ming Lei and Maria Ott and Magnus Wolf-Watz and Timothy David Fenn and Edwin Pozharski and Mark A. Wilson and Gregory A. Petsko and Martin Karplus and Christian Gerhard H{\"u}bner and Dorothee Kern},
  journal={Nature},
  year={2007},
  volume={450},
  pages={838-844}
}
The mechanisms by which enzymes achieve extraordinary rate acceleration and specificity have long been of key interest in biochemistry. It is generally recognized that substrate binding coupled to conformational changes of the substrate–enzyme complex aligns the reactive groups in an optimal environment for efficient chemistry. Although chemical mechanisms have been elucidated for many enzymes, the question of how enzymes achieve the catalytically competent state has only recently become… Expand

Paper Mentions

Blog Post
Dynamic Connection between Enzymatic Catalysis and Collective Protein Motions.
TLDR
The results illustrate a linkage between enzymatic catalysis and collective protein motions, whereby the disparate time scales between the two processes are bridged by a cascade of intermediate-scale motion of catalytic residues modulating the free energy landscapes of the catalytic and conformational change processes. Expand
Conformational state distributions and catalytically relevant dynamics of a hinge-bending enzyme studied by single-molecule FRET and a coarse-grained simulation.
TLDR
From single-molecule Förster resonance energy transfer, insight is obtained into the distribution of conformational states and the dynamical properties of the domains of phosphoglycerate kinase, showing that PGK is intrinsically a highly dynamic system sampling a wealth of conformations on timescales ranging from nanoseconds to milliseconds and above. Expand
Direct observation of ultrafast large-scale dynamics of an enzyme under turnover conditions
TLDR
It is proposed that ultrafast domain closure is used by enzymes as a mechanism to optimize mutual orientation of substrates, a novel mode of coupling between conformational dynamics and catalysis, and a paradigm for the mode of action of enzymes is proposed. Expand
Coupling between Catalytic Loop Motions and Enzyme Global Dynamics
TLDR
An extensive study on a set of enzymes to assess whether the collective/global dynamics, as predicted by elastic network models (ENMs), facilitates or even defines the local motions undergone by functional loops suggests that robust global modes cooperatively defined by the overall enzyme architecture also entail local components that assist in suitable opening/closure of the catalytic loop over the active site. Expand
Subnanometre enzyme mechanics probed by single-molecule force spectroscopy
TLDR
These results, combining experiment and molecular dynamics simulations, give detailed mechanical insights into how an enzyme can cope with the seemingly contradictory requirements of rapid substrate exchange and tight closing, to ensure efficient catalysis. Expand
Mix-and-inject XFEL crystallography reveals gated conformational dynamics during enzyme catalysis
TLDR
It is demonstrated that MISC can capture otherwise elusive aspects of enzyme mechanism and dynamics in microcrystalline samples, resolving long-standing questions about the connection between nonequilibrium protein motions and enzyme catalysis. Expand
A hierarchy of timescales in protein dynamics is linked to enzyme catalysis
TLDR
It is shown that pico- to nano-second timescale atomic fluctuations in hinge regions of adenylate kinase facilitate the large-scale, slower lid motions that produce a catalytically competent state. Expand
Structural basis for ligand binding to an enzyme by a conformational selection pathway
TLDR
A molecular description of a high-energy enzyme state in a conformational selection pathway is presented by an experimental strategy centered on NMR spectroscopy, protein engineering, and X-ray crystallography and it is discovered that the structural sampling of the substrate free enzyme corresponds to the complete amplitude that is associated with formation of the closed and catalytically active state. Expand
Probing conformational dynamics of an enzymatic active site by an in situ single fluorogenic probe under piconewton force manipulation
TLDR
This study interrogated the conformational dynamics of horseradish peroxidase using single-molecule multiparameter photon time-stamping spectroscopy with mechanical force manipulation, a newly developed single- molecule fluorescence imaging magnetic tweezers nanoscopic approach, and a nascent-formed fluorogenic product molecule serves as a probe. Expand
Conformational sampling, catalysis, and evolution of the bacterial phosphotriesterase
TLDR
“open” and “closed” CSs in PTE and dominant structural transition in the enzyme that links them are identified and analysis of the structural and kinetic effects of mutations distant from the active site suggests that remote mutations affect the turnover rate by altering the conformational landscape. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 104 REFERENCES
Intrinsic dynamics of an enzyme underlies catalysis
TLDR
It is shown that the intrinsic plasticity of the protein is a key characteristic of catalysis, and the pre-existence of collective dynamics in enzymes before catalysis is a common feature of biocatalysts and that proteins have evolved under synergy pressure between structure and dynamics. Expand
A hierarchy of timescales in protein dynamics is linked to enzyme catalysis
TLDR
It is shown that pico- to nano-second timescale atomic fluctuations in hinge regions of adenylate kinase facilitate the large-scale, slower lid motions that produce a catalytically competent state. Expand
Adenylate kinase motions during catalysis: an energetic counterweight balancing substrate binding.
TLDR
The comparison of two very different conformations of the same polypeptide chain revealed kinematic details of the catalytic cycle and indicated that there exists an energetic counterweight compensating the substrate binding energy required for specificity. Expand
Relating protein motion to catalysis.
TLDR
This review examines the linkage between protein conformational motions and enzyme catalysis in the context of two enzymes that catalyze hydride transfer, namely dihydrofolate reductase and liver alcohol dehydrogenase. Expand
Movie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases.
TLDR
Given the proliferating number of homologous proteins known to exist in different conformational states, it is becoming possible to outline the motions of chain segments and combine them into a movie, which can then represent protein action much more effectively than static pictures alone are able to do. Expand
Studying excited states of proteins by NMR spectroscopy
TLDR
Novel relaxation dispersion NMR techniques are used to kinetically and thermodynamically characterize a transition between a highly populated ground state conformation and an excited state that is 2.0 kcal mol−1 higher in free energy. Expand
Nonlinear elasticity, proteinquakes, and the energy landscapes of functional transitions in proteins
TLDR
This work presents a model for global structural transformations, such as allostery, that involve large-scale motion and possible partial unfolding, illustrating the method with the conformational transition of adenylate kinase. Expand
Dynamics of the flexible loop of triosephosphate isomerase: the loop motion is not ligand gated.
TLDR
Surprisingly, spectra of TIM ligated with a substrate analog, glycerol 3-phosphate (G3P), or with a tight-binding transition-state analog, phosphoglycolate (PGA), show that the loop moves with a rate similar to the rate in the empty enzyme and also has a similar population ratio for the two conformers. Expand
Linkage between dynamics and catalysis in a thermophilic-mesophilic enzyme pair
TLDR
A comparative and quantitative study of activity, structure and dynamics revealed a close link between protein dynamics and catalytic turnover in hyperthermophilic and mesophilic homologs of adenylate kinase. Expand
Probing the free-energy surface for protein folding with single-molecule fluorescence spectroscopy
TLDR
It is shown that single-molecule FRET measurements of a small cold-shock protein expose equilibrium collapse of the unfolded polypeptide and allow us to calculate limits on the polyPEptide reconfiguration time. Expand
...
1
2
3
4
5
...