1e37: Difference between revisions
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'''PORCINE PANCREATIC ELASTASE COMPLEXED WITH (3S, 4S)N-PARA-NITROBENZENESULPHONYL-3-ETHYL-4-(CARBOXYLIC ACID)PYRROLIDIN-2-ONE SOAKED IN PH 9 BUFFER FOR 1 MINUTE''' | '''PORCINE PANCREATIC ELASTASE COMPLEXED WITH (3S, 4S)N-PARA-NITROBENZENESULPHONYL-3-ETHYL-4-(CARBOXYLIC ACID)PYRROLIDIN-2-ONE SOAKED IN PH 9 BUFFER FOR 1 MINUTE''' | ||
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[[Category: Wilmouth, R C.]] | [[Category: Wilmouth, R C.]] | ||
[[Category: Wright, P A.]] | [[Category: Wright, P A.]] | ||
[[Category: | [[Category: Hydrolase]] | ||
[[Category: | [[Category: Serine protease]] | ||
[[Category: | [[Category: Serine proteinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:36:13 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 14:36, 2 May 2008
PORCINE PANCREATIC ELASTASE COMPLEXED WITH (3S, 4S)N-PARA-NITROBENZENESULPHONYL-3-ETHYL-4-(CARBOXYLIC ACID)PYRROLIDIN-2-ONE SOAKED IN PH 9 BUFFER FOR 1 MINUTE
OverviewOverview
beta-Lactams inhibit a range of enzymes via acylation of nucleophilic serine residues. Certain gamma-lactam analogues of monocyclic beta-lactams have also been shown to be reversible inhibitors of porcine pancreatic elastase (PPE), forming acyl-enzyme complexes that are stable with respect to hydrolysis. Crystallographic analysis at pH 5 of an acyl-enzyme complex formed with PPE and one of these inhibitors revealed the ester carbonyl located in the oxyanion hole in a similar conformation to that observed in the structure of a complex formed between a heptapeptide (beta-casomorphin-7) and PPE. Only weak electron density was observed for the His-57 side chain in its 'native' conformation. Instead, the His-57 side chain predominantly adopted a conformation rotated approx. 90 degrees from its normal position. PPE-gamma-lactam crystals were subjected to 'pH-jumps' by placing the crystals in a buffer of increased pH prior to freezing for data collection. The results indicate that the conformation of the gamma-lactam-derived acyl-enzyme species in the PPE active site is dependent on pH, a result having implications for the analysis of other serine protease-inhibitor structures at non-catalytic pH values. The results help to define the stereoelectronic relationship between the ester of the acyl-enzyme complex, the side chain of His-57 and the incoming nucleophile during the reversible (de)acylation steps, implying it is closely analogous to the hydrolytic deacylation step during catalytic peptide hydrolysis.
About this StructureAbout this Structure
1E37 is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.
ReferenceReference
'pH-jump' crystallographic analyses of gamma-lactam-porcine pancreatic elastase complexes., Wright PA, Wilmouth RC, Clifton IJ, Schofield CJ, Biochem J. 2000 Oct 15;351 Pt 2:335-40. PMID:11023818 Page seeded by OCA on Fri May 2 14:36:13 2008