1h2y | pdb_00001h2y

PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, Y473F MUTANT WITH COVALENTLY BOUND INHIBITOR Z-PRO-PROLINAL

spinqualitylabelsall models 1h2y, resolution 1.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1h2y is a 1 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.78Å Ligands: GOL, ZPR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PPCE_PIG Cleaves peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Prolyl oligopeptidase, a member of a new family of serine peptidases, plays an important role in memory disorders. Earlier x-ray crystallographic investigations indicated that stabilization of the tetrahedral transition state of the reaction involved hydrogen bond formation between the oxyanion of the tetrahedral intermediate and the OH group of Tyr(473). The contribution of the OH group was tested with the Y473F variant using various substrates. The charged succinyl-Gly-Pro-4-nitroanilide was hydrolyzed with a much lower k(cat)/K(m) compared with the neutral benzyloxycarbonyl-G1y-Pro-2-naphthylamide, although the binding modes of the two substrates were similar, as shown by x-ray crystallography. This suggested that electrostatic interactions between Arg(643) and the succinyl group competed with the productive binding mechanism. Unlike most enzyme reactions, catalysis by the wild-type enzyme exhibited positive activation entropy. In contrast, the activation entropy for the Y473F variant was negative, suggesting that the tyrosine OH group is involved in stabilizing both the transition state and the water shell at the active site. Importantly, Tyr(473) is also implicated in the formation of the enzyme-substrate complex. The nonlinear Arrhenius plot suggested a greater significance of the oxyanion binding site at physiological temperature. The results indicated that Tyr(473) was more needed at high pH, at high temperature, and with charged substrates exhibiting "internally competitive inhibition." Electrostatic effects and binding determinants in the catalysis of prolyl oligopeptidase. Site specific mutagenesis at the oxyanion binding site.,Szeltner Z, Rea D, Renner V, Fulop V, Polgar L J Biol Chem. 2002 Nov 8;277(45):42613-22. Epub 2002 Aug 28. PMID:12202494 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Prolyl Endopeptidase

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