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| - | [[Image:7tln.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_7tln| PDB=7tln | SCENE= }} | | {{STRUCTURE_7tln| PDB=7tln | SCENE= }} |
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| - | '''STRUCTURAL ANALYSIS OF THE INHIBITION OF THERMOLYSIN BY AN ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITOR'''
| + | ===STRUCTURAL ANALYSIS OF THE INHIBITION OF THERMOLYSIN BY AN ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITOR=== |
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| - | ==Overview==
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| - | The mode of binding of the irreversible thermolysin inhibitor ClCH2CO-DL-(N-OH)Leu-OCH3 [Rasnick, D., & Powers, J.C. (1978) Biochemistry 17, 4363-4369] has been determined by X-ray crystallography at a resolution of 2.3 A and the structure of the covalent complex refined to give a crystallographic residual of 17.0%. This is the first such structural study of an active-site-directed covalent complex of a zinc protease. As anticipated by Rasnick and Powers, the inhibitor alkylates Glu-143 in the thermolysin active site, and the hydroxamic acid moiety coordinates the zinc ion. The formation of the covalent complex is associated with a significant shift in a segment of the polypeptide backbone in the vicinity of the active site. This conformational adjustment appears to be necessary to relieve steric hindrance which would otherwise prevent alkylation of Glu-143. It is suggested that this steric hindrance, which occurs for thermolysin but would not be expected for carboxypeptidase A, accounts for the previously inexplicable difference in reactivity of these two metalloproteases toward N-haloacetyl amino acids. The relevance of this steric hindrance to the mechanism of catalysis is discussed. In agreement with previous results [Kester, W. R., & Matthews, B. W. (1977) Biochemistry 16, 2506-2516], it appears that steric hindrance prevents the direct attack of Glu-143 on the carbonyl carbon of an extended substrate, therefore ruling out the anhydride pathway in thermolysin-catalyzed hydrolysis of polypeptide substrates and their ester analogues.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_6830761}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 6830761 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_6830761}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Matthews, B W.]] | | [[Category: Matthews, B W.]] |
| | [[Category: Tronrud, D E.]] | | [[Category: Tronrud, D E.]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 22:47:58 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul 3 15:14:36 2008'' |
Revision as of 12:15, 3 July 2008
Template:STRUCTURE 7tln
STRUCTURAL ANALYSIS OF THE INHIBITION OF THERMOLYSIN BY AN ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITOR
Template:ABSTRACT PUBMED 6830761
About this Structure
7TLN is a Single protein structure of sequence from Bacillus thermoproteolyticus. This structure supersedes the now removed PDB entry 6tln. Full crystallographic information is available from OCA.
Reference
Structural analysis of the inhibition of thermolysin by an active-site-directed irreversible inhibitor., Holmes MA, Tronrud DE, Matthews BW, Biochemistry. 1983 Jan 4;22(1):236-40. PMID:6830761
Page seeded by OCA on Thu Jul 3 15:14:36 2008
