2RGX

Crystal Structure of Adenylate Kinase from Aquifex Aeolicus in complex with Ap5A

Summary for 2RGX

• Entry DOI: 10.2210/pdb2rgx/pdb
• Related: 2RH5
• Descriptor: Adenylate kinase, ZINC ION, BIS(ADENOSINE)-5'-PENTAPHOSPHATE, ... (4 entities in total)
• Functional Keywords: transferase(phosphotransferase), atp-binding, kinase, nucleotide-binding, transferase
• Biological source: Aquifex aeolicus
• Cellular location: Cytoplasm : O66490
• Total number of polymer chains: 1
• Total formula weight: 24447.06

Authors

Thai, V.,Wolf-Watz, M.,Fenn, T.,Pozharski, E.,Wilson, M.A.,Petsko, G.A.,Kern, D. (deposition date: 2007-10-05, release date: 2007-12-18, Last modification date: 2023-08-30)

Primary citation

Henzler-Wildman, K.A.,Thai, V.,Lei, M.,Ott, M.,Wolf-Watz, M.,Fenn, T.,Pozharski, E.,Wilson, M.A.,Petsko, G.A.,Karplus, M.,Hubner, C.G.,Kern, D.
Intrinsic motions along an enzymatic reaction trajectory.
Nature, 450:838-844, 2007

PubMed Abstract: 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.

PubMed: 18026086
DOI: 10.1038/nature06410

Experimental method

X-RAY DIFFRACTION (1.9 Å)