Intrinsic motions along an enzymatic reaction trajectory. Export

@article{citeulike:1939399, 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.}, author = {Henzler-Wildman, Katherine A. and Thai, Vu and Lei, Ming and Ott, Maria and Wolf-Watz, Magnus and Fenn, Tim and Pozharski, Ed and Wilson, Mark A. and Petsko, Gregory A. and Karplus, Martin and H\"{u}bner, Christian G. and Kern, Dorothee}, citeulike-article-id = {1939399}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature06410}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature06410}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18026086}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18026086}, day = {6}, doi = {10.1038/nature06410}, issn = {1476-4687}, journal = {Nature}, keywords = {dynamics, energy\_landscape, enzyme, protein}, month = {December}, number = {7171}, pages = {838--844}, posted-at = {2008-10-31 13:45:36}, priority = {2}, publisher = {Nature Publishing Group}, title = {Intrinsic motions along an enzymatic reaction trajectory.}, url = {http://dx.doi.org/10.1038/nature06410}, volume = {450}, year = {2007} }

TY - JOUR ID - citeulike:1939399 L3 - citeulike-article-id:1939399 N2 - 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. IS - 7171 JF - Nature SN - 1476-4687 EP - 844 TI - Intrinsic motions along an enzymatic reaction trajectory. PB - Nature Publishing Group VL - 450 SP - 838 KW - dynamics KW - energy_landscape KW - enzyme KW - protein AU - Henzler-Wildman, Katherine AU - Thai, Vu AU - Lei, Ming AU - Ott, Maria AU - Wolf-Watz, Magnus AU - Fenn, Tim AU - Pozharski, Ed AU - Wilson, Mark AU - Petsko, Gregory AU - Karplus, Martin AU - Hübner, Christian AU - Kern, Dorothee PY - 2007/12/06/ UR - http://dx.doi.org/10.1038/nature06410 ER -