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| - | [[Image:1h2x.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1h2x| PDB=1h2x | SCENE= }} | | {{STRUCTURE_1h2x| PDB=1h2x | SCENE= }} |
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| - | '''PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, Y473F MUTANT'''
| + | ===PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, Y473F MUTANT=== |
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| - | ==Overview==
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| - | 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."
| + | The line below this paragraph, {{ABSTRACT_PUBMED_12202494}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 12202494 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_12202494}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Prolyl oligopeptidase]] | | [[Category: Prolyl oligopeptidase]] |
| | [[Category: Serine protease]] | | [[Category: Serine protease]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:21:47 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 06:32:13 2008'' |
Revision as of 03:32, 1 July 2008
Template:STRUCTURE 1h2x
PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, Y473F MUTANT
Template:ABSTRACT PUBMED 12202494
About this Structure
1H2X is a Single protein structure. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Tue Jul 1 06:32:13 2008
