View source for 7tln


==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]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7tln]] is a 1 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=7TLN FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7tln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tln OCA], [https://pdbe.org/7tln PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tln RCSB], [https://www.ebi.ac.uk/pdbsum/7tln PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tln ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/THER_BACTH THER_BACTH] Extracellular zinc metalloprotease.
== 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/main_output.php?pdb_ID=7tln ConSurf].
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== Publication Abstract from PubMed ==
The mode of binding of the irreversible thermolysin inhibitor ClCH2CO-DL-(N-OH)Leu-OCH3 [Rasnick, D., &amp; 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., &amp; 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7tln" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thermolysin 3D structures|Thermolysin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus thermoproteolyticus]]
[[Category: Large Structures]]
[[Category: Holmes MA]]
[[Category: Matthews BW]]
[[Category: Tronrud DE]]