Document Detail


Synergistic effects of substrate-induced conformational changes in phosphoglycerate kinase activation.
MedLine Citation:
PMID:  9000079     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phosphoglycerate kinase (PGK), a key enzyme in glycolysis, catalyses the transfer of a phosphoryl-group from 1,3-bisphosphoglycerate to ADP to form 3-phosphoglycerate and ATP. Despite extensive kinetic and structural investigations over more than two decades, the conformation assumed by this enzyme during catalysis remained unknown. Here we present the 2.8 A crystal structure of a ternary complex of PGK from Trypanosoma brucei, the causative agent of sleeping sickness. This structure determination relied on a procedure in which fragments containing less than 10% of the scattering mass were successively positioned in the unit cell to obtain phases. The PGK ternary complex exhibits a dramatic closing of the large cleft between the two domains seen in all previous studies, thereby bringing the two ligands, 3-phosphoglycerate and ADP into close proximity. Our results demonstrate that PGK is a hinge-bending enzyme, reveal a novel mechanism in which substrate-induced effects combine synergistically to induce major conformational changes and, to our knowledge, afford the first observation of the PGK active site in a catalytic conformation.
Authors:
B E Bernstein; P A Michels; W G Hol
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  385     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-02-06     Completed Date:  1997-02-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  275-8     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Biomolecular Structure Center, University of Washington, Seattle 98195, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Diphosphate / metabolism
Allosteric Regulation
Animals
Binding Sites
Catalysis
Crystallography, X-Ray
Enzyme Activation
Escherichia coli
Glyceric Acids / metabolism
Models, Molecular
Phosphoglycerate Kinase / chemistry*,  metabolism
Protein Conformation*
Recombinant Proteins / chemistry
Trypanosoma brucei brucei / enzymology
Chemical
Reg. No./Substance:
0/Glyceric Acids; 0/Recombinant Proteins; 58-64-0/Adenosine Diphosphate; 820-11-1/3-phosphoglycerate; EC 2.7.2.3/Phosphoglycerate Kinase
Comments/Corrections
Comment In:
Nature. 1997 Jan 16;385(6613):204-5   [PMID:  9000067 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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