1e8m

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{{STRUCTURE_1e8m| PDB=1e8m | SCENE= }}
{{STRUCTURE_1e8m| PDB=1e8m | SCENE= }}
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'''PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, MUTANT, COMPLEXED WITH INHIBITOR'''
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===PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, MUTANT, COMPLEXED WITH INHIBITOR===
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==Overview==
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Structure determination of the inactive S554A variant of prolyl oligopeptidase complexed with an octapeptide has shown that substrate binding is restricted to the P4-P2' region. In addition, it has revealed a hydrogen bond network of potential catalytic importance not detected in other serine peptidases. This involves a unique intramolecular hydrogen bond between the P1' amide and P2 carbonyl groups and another between the P2' amide and Nepsilon2 of the catalytic histidine 680 residue. It is argued that both hydrogen bonds promote proton transfer from the imidazolium ion to the leaving group. Another complex formed with the product-like inhibitor benzyloxycarbonyl-glycyl-proline, indicating that the carboxyl group of the inhibitor forms a hydrogen bond with the Nepsilon2 of His(680). Because a protonated histidine makes a stronger interaction with the carboxyl group, it offers a possibility of the determination of the real pK(a) of the catalytic histidine residue. This was found to be 6.25, lower than that of the well studied serine proteases. The new titration method gave a single pK(a) for prolyl oligopeptidase, whose reaction exhibited a complex pH dependence for k(cat)/K(m), and indicated that the observed pK(a) values are apparent. The procedure presented may be applicable for other serine peptidases.
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{{ABSTRACT_PUBMED_11031266}}
==About this Structure==
==About this Structure==
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[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Prolyl oligopeptidase]]
[[Category: Prolyl oligopeptidase]]
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Revision as of 21:19, 30 June 2008

Image:1e8m.png

Template:STRUCTURE 1e8m

PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, MUTANT, COMPLEXED WITH INHIBITOR

Template:ABSTRACT PUBMED 11031266

About this Structure

1E8M is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.

Reference

Structures of prolyl oligopeptidase substrate/inhibitor complexes. Use of inhibitor binding for titration of the catalytic histidine residue., Fulop V, Szeltner Z, Renner V, Polgar L, J Biol Chem. 2001 Jan 12;276(2):1262-6. PMID:11031266

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