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| | {{STRUCTURE_1o6f| PDB=1o6f | SCENE= }} | | {{STRUCTURE_1o6f| PDB=1o6f | SCENE= }} |
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| - | '''PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, D641A MUTANT WITH BOUND PEPTIDE LIGAND SUC-GLY-PRO'''
| + | ===PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, D641A MUTANT WITH BOUND PEPTIDE LIGAND SUC-GLY-PRO=== |
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| - | ==Overview==
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| - | Prolyl oligopeptidase, a serine peptidase unrelated to trypsin and subtilisin, is implicated in memory disorders and is an important target of drug design. The catalytic competence of the Asp(641) residue of the catalytic triad (Ser(554), Asp(641), His(680)) was studied using the D641N and D641A variants of the enzyme. Both variants displayed 3 orders of magnitude reduction in k(cat)/K(m) for benzyloxycarbonyl-Gly-Pro-2-naphthylamide. Using an octapeptide substrate, the decrease was 6 orders of magnitude, whereas with Z-Gly-Pro-4-nitrophenyl ester there was virtually no change in k(cat)/K(m). This indicates that the contribution of Asp(641) is very much dependent on the substrate-leaving group, which was not the case for the classic serine peptidase, trypsin. The rate constant for benzyloxycarbonyl-Gly-Pro-thiobenzylester conformed to this series as demonstrated by a method designed for monitoring the hydrolysis of thiolesters in the presence of thiol groups. Alkylation of His(680) with Z-Gly-Pro-CH(2)Cl was concluded with similar rate constants for wild-type and D641A variant. However, kinetic measurements with Z-Gly-Pro-OH, a product-like inhibitor, indicated that the His(680) is not accessible in the enzyme variants. Crystal structure determination of these mutants revealed subtle perturbations related to the catalytic activity. Many of these observations show differences in the catalysis between trypsin and prolyl oligopeptidase.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_12228249}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 12228249 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_12228249}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Hydrolase]] | | [[Category: Hydrolase]] |
| | [[Category: Prolyl oligopeptidase]] | | [[Category: Prolyl oligopeptidase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:26:29 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:11:15 2008'' |
Revision as of 17:11, 28 July 2008
Template:STRUCTURE 1o6f
PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, D641A MUTANT WITH BOUND PEPTIDE LIGAND SUC-GLY-PRO
Template:ABSTRACT PUBMED 12228249
About this Structure
1O6F is a Single protein structure. Full crystallographic information is available from OCA.
Reference
Substrate-dependent competency of the catalytic triad of prolyl oligopeptidase., Szeltner Z, Rea D, Juhasz T, Renner V, Mucsi Z, Orosz G, Fulop V, Polgar L, J Biol Chem. 2002 Nov 22;277(47):44597-605. Epub 2002 Sep 11. PMID:12228249
Page seeded by OCA on Mon Jul 28 20:11:15 2008
