2p9c
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Crystal structure of serine bound G336V mutant of E.coli phosphoglycerate dehydrogenase
OverviewOverview
d-3-Phosphoglycerate dehydrogenase (EC 1.1.1.95) from Escherichia coli, contains two Gly-Gly sequences that have been shown previously to have the, characteristics of hinge regions. One of these, Gly(336)-Gly(337), is, found in the loop between the substrate binding domain and the regulatory, domain. Changing these glycine residues to valine affected the sensitivity, of the enzyme to inhibition by l-serine but not the extent of inhibition., The decrease in sensitivity was caused primarily by a decrease in the, affinity of the enzyme for l-serine. These mutations also affected the, domain rotation of the subunits in response to l-serine binding. A major, conclusion of this study was that it defines a minimal limit on the, necessary conformational changes leading to inhibition of enzyme activity., That is, some of the conformational differences seen in the native enzyme, upon l-serine binding are not critical for inhibition, whereas others are, maintained and may play important roles in inhibition and cooperativity., The structure of G336V demonstrates that the minimal effect of l-serine, binding leading to inhibition of enzyme activity requires a domain, rotation of approximately only 6 degrees in just two of the four subunits, of the enzyme that are oriented diagonally across from each other in the, tetramer. Moreover the structures show that both pairs of Asn(190) to, Asn(190) hydrogen bonds across the subunit interfaces are necessary for, activity. These observations are consistent with the half-the-sites, activity, flip-flop mechanism proposed for this and other similar enzymes, and suggest that the Asn(190) hydrogen bonds may function in the, conformational transition between alternate half-the-site active forms of, the enzyme.
About this StructureAbout this Structure
2P9C is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as Phosphoglycerate dehydrogenase, with EC number 1.1.1.95 Full crystallographic information is available from OCA.
ReferenceReference
The Effect of Hinge Mutations on Effector Binding and Domain Rotation in Escherichia coli D-3-Phosphoglycerate Dehydrogenase., Dey S, Hu Z, Xu XL, Sacchettini JC, Grant GA, J Biol Chem. 2007 Jun 22;282(25):18418-26. Epub 2007 Apr 24. PMID:17459882
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