| Role of induced fit in enzyme specificity: a molecular forward/reverse switch. | |
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MedLine Citation:
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PMID: 18544537 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Enzyme structures solved with and without bound substrate often show that substrate-induced conformational changes bring catalytic residues into alignment, alter the local environment, and position the substrate for catalysis. Although the structural data are compelling, the role of conformational changes in enzyme specificity has been controversial in that specificity is a kinetic property that is not easy to predict based upon structure alone. Recent studies on DNA polymerization have illuminated the role of substrate-induced conformational changes in enzyme specificity by showing that the rate at which the enzyme opens to release the bound substrate is a key kinetic parameter. The slow release of a correct substrate commits it to the forward reaction so that specificity is determined solely by the rate of substrate binding, including the isomerization step, and not by the slower rate of the chemical reaction. In contrast, fast dissociation of an incorrect substrate favors release rather than reaction. Thus, the conformational change acts as a molecular switch to select the right substrate and to recognize and disfavor the reaction of an incorrect substrate. A conformational switch may also favor release rather than reverse reaction of the product. |
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Authors:
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Kenneth A Johnson |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review Date: 2008-06-10 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 283 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-09-22 Completed Date: 2008-11-10 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 26297-301 Citation Subset: IM |
Affiliation:
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Department of Chemistry and Biochemistry, Institute of Cellular and Molecular Biology, University of Texas, Austin, Texas 78712, USA. kajohnson@mail.utexas.edu |
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| MeSH Terms | |
Descriptor/Qualifier:
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Bacteriophage T7
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enzymology* DNA Replication / physiology* DNA-Directed DNA Polymerase / chemistry* Kinetics Models, Chemical* Protein Conformation Substrate Specificity / physiology Viral Proteins / chemistry* |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM071404/GM/NIGMS NIH HHS; R01 GM071404-04/GM/NIGMS NIH HHS; R01 GM084741-03/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Viral Proteins; EC 2.7.7.-/bacteriophage T7 induced DNA polymerase; EC 2.7.7.7/DNA-Directed DNA Polymerase |
| Comments/Corrections | |
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