Intrinsic motions along an enzymatic reaction trajectory

Katherine A. Henzler-Wildman, Vu Thai, Ming Lei, Maria Ott, Magnus Wolf-Watz, Tim Fenn, Ed Pozharski, Mark A. Wilson, Gregory A. Petsko, Martin Karplus, Christian G. Hübner () and Dorothee Kern ()
Additional contact information
Katherine A. Henzler-Wildman: Department of Biochemistry and Howard Hughes Medical Institute,
Vu Thai: Department of Biochemistry and Howard Hughes Medical Institute,
Ming Lei: Department of Biochemistry and Howard Hughes Medical Institute,
Maria Ott: Institute of Physics, Martin Luther-University Halle-Wittenberg, D-06120 Halle, Germany
Magnus Wolf-Watz: Department of Biochemistry and Howard Hughes Medical Institute,
Tim Fenn: Brandeis University, Waltham, Massachusetts 02454, USA
Ed Pozharski: Brandeis University, Waltham, Massachusetts 02454, USA
Mark A. Wilson: Brandeis University, Waltham, Massachusetts 02454, USA
Gregory A. Petsko: Brandeis University, Waltham, Massachusetts 02454, USA
Martin Karplus: Harvard University, Cambridge, Massachusetts 02138, USA
Christian G. Hübner: Institute of Physics, Martin Luther-University Halle-Wittenberg, D-06120 Halle, Germany
Dorothee Kern: Department of Biochemistry and Howard Hughes Medical Institute,

Nature, 2007, vol. 450, issue 7171, 838-844

Abstract: 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.

Date: 2007
References: Add references at CitEc
Citations: View citations in EconPapers (10)

Downloads: (external link)
https://www.nature.com/articles/nature06410 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:450:y:2007:i:7171:d:10.1038_nature06410

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature06410

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().