Document Detail

Comparison of AMP and NADH binding to glycogen phosphorylase b.
MedLine Citation:
PMID:  6415289     Owner:  NLM     Status:  MEDLINE    
The binding sites for the allosteric activator, AMP, to glycogen phosphorylase b are described in detail utilizing the more precise knowledge of the native structure obtained from crystallographic restrained least-squares refinement than has hitherto been available. Localized conformational changes are seen at the allosteric effector site that include shifts of between 1 and 2 A for residues Tyr75 and Arg309 and very small shifts for the region of residues 42 to 44 from the symmetry-related subunit. Kinetic studies demonstrate that NADH inhibits the AMP activation of glycogen phosphorylase b. Crystallographic binding studies at 3.5 A resolution show that NADH binds to the same sites on the enzyme as AMP, i.e. the allosteric effector site N, which is close to the subunit-subunit interface, and the nucleoside inhibitor site I, which is some 12 A from the catalytic site. The conformations of NADH at the two sites are different but both conformations are "folded" so that the nicotinamide ring is close (approx. 6 A) to the adenine ring. These conformations are compared with those suggested from solution studies and with the extended conformations observed in the single crystal structure of NAD+ and for NAD bound to dehydrogenases. Possible mechanisms for NADH inhibition of phosphorylase activation are discussed.
E A Stura; G Zanotti; Y S Babu; M S Sansom; D I Stuart; K S Wilson; L N Johnson; G Van de Werve
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of molecular biology     Volume:  170     ISSN:  0022-2836     ISO Abbreviation:  J. Mol. Biol.     Publication Date:  1983 Oct 
Date Detail:
Created Date:  1983-12-17     Completed Date:  1983-12-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985088R     Medline TA:  J Mol Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  529-65     Citation Subset:  IM    
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MeSH Terms
Adenosine Monophosphate / metabolism*
Allosteric Site
Binding Sites
Enzyme Activation / drug effects
Macromolecular Substances
Molecular Conformation
NAD / metabolism*
Phosphorylase b / metabolism*
Phosphorylases / metabolism*
Protein Conformation
Reg. No./Substance:
0/Macromolecular Substances; 53-84-9/NAD; 61-19-8/Adenosine Monophosphate; EC 2.4.1.-/Phosphorylase b; EC 2.4.1.-/Phosphorylases

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

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