2rgx
From Proteopedia
(New page: 200px<br /><applet load="2rgx" size="350" color="white" frame="true" align="right" spinBox="true" caption="2rgx, resolution 1.900Å" /> '''Crystal Structure o...) |
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==Overview== | ==Overview== | ||
| - | The mechanisms by which enzymes achieve extraordinary rate acceleration | + | 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 approachable by experiment and computation. Here we show crystallographic evidence for conformational substates along the trajectory towards the catalytically competent 'closed' state in the ligand-free form of the enzyme adenylate kinase. Molecular dynamics simulations indicate that these partially closed conformations are sampled in nanoseconds, whereas nuclear magnetic resonance and single-molecule fluorescence resonance energy transfer reveal rare sampling of a fully closed conformation occurring on the microsecond-to-millisecond timescale. Thus, the larger-scale motions in substrate-free adenylate kinase are not random, but preferentially follow the pathways that create the configuration capable of proficient chemistry. Such preferred directionality, encoded in the fold, may contribute to catalysis in many enzymes. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Fenn, T]] | [[Category: Fenn, T]] | ||
[[Category: Kern, D.]] | [[Category: Kern, D.]] | ||
| - | [[Category: Petsko, G | + | [[Category: Petsko, G A.]] |
[[Category: Pozharski, E.]] | [[Category: Pozharski, E.]] | ||
[[Category: Thai, V.]] | [[Category: Thai, V.]] | ||
| - | [[Category: Wilson, M | + | [[Category: Wilson, M A.]] |
[[Category: Wolf-Watz, M.]] | [[Category: Wolf-Watz, M.]] | ||
[[Category: AP5]] | [[Category: AP5]] | ||
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[[Category: transferase(phosphotransferase)]] | [[Category: transferase(phosphotransferase)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:47:17 2008'' |
Revision as of 16:47, 21 February 2008
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Crystal Structure of Adenylate Kinase from Aquifex Aeolicus in complex with Ap5A
Overview
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 approachable by experiment and computation. Here we show crystallographic evidence for conformational substates along the trajectory towards the catalytically competent 'closed' state in the ligand-free form of the enzyme adenylate kinase. Molecular dynamics simulations indicate that these partially closed conformations are sampled in nanoseconds, whereas nuclear magnetic resonance and single-molecule fluorescence resonance energy transfer reveal rare sampling of a fully closed conformation occurring on the microsecond-to-millisecond timescale. Thus, the larger-scale motions in substrate-free adenylate kinase are not random, but preferentially follow the pathways that create the configuration capable of proficient chemistry. Such preferred directionality, encoded in the fold, may contribute to catalysis in many enzymes.
About this Structure
2RGX is a Single protein structure of sequence from Aquifex aeolicus with and as ligands. Active as Adenylate kinase, with EC number 2.7.4.3 Full crystallographic information is available from OCA.
Reference
Intrinsic motions along an enzymatic reaction trajectory., Henzler-Wildman KA, Thai V, Lei M, Ott M, Wolf-Watz M, Fenn T, Pozharski E, Wilson MA, Petsko GA, Karplus M, Hubner CG, Kern D, Nature. 2007 Dec 6;450(7171):838-44. Epub 2007 Nov 18. PMID:18026086
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