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| | {{STRUCTURE_2gmt| PDB=2gmt | SCENE= }} | | {{STRUCTURE_2gmt| PDB=2gmt | SCENE= }} |
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| - | '''THREE-DIMENSIONAL STRUCTURE OF CHYMOTRYPSIN INACTIVATED WITH (2S) N-ACETYL-L-ALANYL-L-PHENYLALANYL-CHLOROETHYL KETONE: IMPLICATIONS FOR THE MECHANISM OF INACTIVATION OF SERINE PROTEASES BY CHLOROKETONES'''
| + | ===THREE-DIMENSIONAL STRUCTURE OF CHYMOTRYPSIN INACTIVATED WITH (2S) N-ACETYL-L-ALANYL-L-PHENYLALANYL-CHLOROETHYL KETONE: IMPLICATIONS FOR THE MECHANISM OF INACTIVATION OF SERINE PROTEASES BY CHLOROKETONES=== |
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| - | ==Overview==
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| - | The reaction of enantiomerically pure (2S)-N-acetyl-L-alanyl-L-phenylalanyl alpha-chloroethane with gamma-chymotrypsin was studied as a probe of the mechanism of inactivation of serine proteases by peptidyl chloroalkanes. It was determined crystallographically that the peptidyl chloroethane alkylates His57 with retention of configuration at the chiral center, indicating a double displacement mechanism. We think it likely that a Ser195-epoxy ether adduct is an intermediate on the inactivation pathway, although other possibilities have not been disproven. Kinetic data reported by others [Angliker et al. (1988) Biochem. J. 256, 481-486] indicate that the epoxy ether intermediate is not an irreversibly inactivated form of enzyme [a conclusion confirmed experimentally (Prorok et al. (1994) Biochemistry 33, 9784-9790)] and that both ring closure of the tetrahedral intermediate to form the epoxy ether and ring opening by His57 partially limit the first-order rate constant for inactivation, ki. The peptidyl chloroethyl derivative adopts a very different active site conformation from that assumed by serine proteases inactivated by peptidyl chloromethanes. Positioning the chloroethyl derivative into the conformation adopted by chloromethyl derivatives would cause the extra methyl group to make a bad van der Waals contact with the inactivator P2 carbonyl carbon, thereby preventing the formation of the invariant hydrogen bond between the inactivator P1 amide nitrogen and the carbonyl group of Ser214. We conclude that the unusual conformation displayed by the chloroethyl derivative is caused by steric hindrance between the extra methyl group and the rest of the inactivator chain. | + | The line below this paragraph, {{ABSTRACT_PUBMED_7947790}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 7947790 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_7947790}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Ringe, D.]] | | [[Category: Ringe, D.]] |
| | [[Category: Steinmetz, A C.U.]] | | [[Category: Steinmetz, A C.U.]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:17:06 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:21:07 2008'' |
Revision as of 00:21, 28 July 2008
Template:STRUCTURE 2gmt
THREE-DIMENSIONAL STRUCTURE OF CHYMOTRYPSIN INACTIVATED WITH (2S) N-ACETYL-L-ALANYL-L-PHENYLALANYL-CHLOROETHYL KETONE: IMPLICATIONS FOR THE MECHANISM OF INACTIVATION OF SERINE PROTEASES BY CHLOROKETONES
Template:ABSTRACT PUBMED 7947790
About this Structure
2GMT is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
Reference
Three-dimensional structure of chymotrypsin inactivated with (2S)-N-acetyl-L-alanyl-L-phenylalanyl alpha-chloroethane: implications for the mechanism of inactivation of serine proteases by chloroketones., Kreutter K, Steinmetz AC, Liang TC, Prorok M, Abeles RH, Ringe D, Biochemistry. 1994 Nov 22;33(46):13792-800. PMID:7947790
Page seeded by OCA on Mon Jul 28 03:21:07 2008
