7tln
From Proteopedia
(Difference between revisions)
Line 1: | Line 1: | ||
- | [[ | + | ==STRUCTURAL ANALYSIS OF THE INHIBITION OF THERMOLYSIN BY AN ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITOR== |
+ | <StructureSection load='7tln' size='340' side='right' caption='[[7tln]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
+ | == Structural highlights == | ||
+ | <table><tr><td colspan='2'>[[7tln]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_thermoproteolyticus Bacillus thermoproteolyticus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6tln 6tln]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TLN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=7TLN FirstGlance]. <br> | ||
+ | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=INC:2-(ACETYL-HYDROXY-AMINO)-4-METHYL-PENTANOIC+ACID+METHYL+ESTER'>INC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
+ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thermolysin Thermolysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.27 3.4.24.27] </span></td></tr> | ||
+ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=7tln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tln OCA], [http://www.rcsb.org/pdb/explore.do?structureId=7tln RCSB], [http://www.ebi.ac.uk/pdbsum/7tln PDBsum]</span></td></tr> | ||
+ | </table> | ||
+ | == Evolutionary Conservation == | ||
+ | [[Image:Consurf_key_small.gif|200px|right]] | ||
+ | Check<jmol> | ||
+ | <jmolCheckbox> | ||
+ | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tl/7tln_consurf.spt"</scriptWhenChecked> | ||
+ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
+ | <text>to colour the structure by Evolutionary Conservation</text> | ||
+ | </jmolCheckbox> | ||
+ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
+ | <div style="clear:both"></div> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | 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. | ||
- | + | 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<ref>PMID:6830761</ref> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | + | </div> | |
- | + | ||
- | + | ||
- | + | ||
- | + | ||
==See Also== | ==See Also== | ||
*[[Thermolysin|Thermolysin]] | *[[Thermolysin|Thermolysin]] | ||
- | + | == References == | |
- | == | + | <references/> |
- | < | + | __TOC__ |
+ | </StructureSection> | ||
[[Category: Bacillus thermoproteolyticus]] | [[Category: Bacillus thermoproteolyticus]] | ||
[[Category: Thermolysin]] | [[Category: Thermolysin]] | ||
- | [[Category: Holmes, M A | + | [[Category: Holmes, M A]] |
- | [[Category: Matthews, B W | + | [[Category: Matthews, B W]] |
- | [[Category: Tronrud, D E | + | [[Category: Tronrud, D E]] |
Revision as of 16:59, 10 December 2014
STRUCTURAL ANALYSIS OF THE INHIBITION OF THERMOLYSIN BY AN ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITOR
|