View source for 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==
<StructureSection load='2gmt' size='340' side='right'caption='[[2gmt]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2gmt]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GMT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GMT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HIN:(2S)+N-ACETYL-L-ALANYL-ALPHAL-PHENYLALANYL-CHLOROETHYLKETONE'>HIN</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=2gmt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gmt OCA], [https://pdbe.org/2gmt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gmt RCSB], [https://www.ebi.ac.uk/pdbsum/2gmt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gmt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CTRA_BOVIN CTRA_BOVIN] 
== 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/gm/2gmt_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=2gmt ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
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.

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<ref>PMID:7947790</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 2gmt" style="background-color:#fffaf0;"></div>

==See Also==
*[[Chymotrypsin 3D structures|Chymotrypsin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Abeles R]]
[[Category: Kreutter K]]
[[Category: Liang T-C]]
[[Category: Prorok M]]
[[Category: Ringe D]]
[[Category: Steinmetz ACU]]