View source for 2v35


==Porcine Pancreatic Elastase in complex with inhibitor JM54==
<StructureSection load='2v35' size='340' side='right'caption='[[2v35]], [[Resolution|resolution]] 1.67&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2v35]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V35 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V35 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]] 1.67&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J54:(2R)-3-{[(BENZYLAMINO)CARBONYL]AMINO}-2-HYDROXYPROPANOIC+ACID'>J54</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2v35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v35 OCA], [https://pdbe.org/2v35 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v35 RCSB], [https://www.ebi.ac.uk/pdbsum/2v35 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v35 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CELA1_PIG CELA1_PIG] Acts upon elastin.
== 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/v3/2v35_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=2v35 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The presence of a leaving group at C-4 of monobactams is usually considered to be a requirement for mechanism-based inhibition of human leukocyte elastase by these acylating agents. We report that second-order rate constants for the alkaline hydrolysis and elastase inactivation by N-carbamoyl monobactams are independent of the pKa of the leaving group at C-4. Indeed, the effect exerted by these substituents is purely inductive: electron-withdrawing substituents at C-4 of N-carbamoyl-3,3-diethylmonobactams increase the rate of alkaline hydrolysis and elastase inactivation, with Hammett pI values of 3.4 and 2.5, respectively, which indicate the development of a negative charge in the transition-states. The difference in magnitude between these pI values is consistent with an earlier transition-state for the enzymatic reaction when compared with that for the chemical process. These results suggest that the rate-limiting step in elastase inactivation is the formation of the tetrahedral intermediate, and that beta-lactam ring-opening is not concerted with the departure of a leaving group from C-4. Monobactam sulfones emerged as potent elastase inhibitors even when the ethyl groups at C-3, required for interaction with the primary recognition site, are absent. For one such compound, a 1 : 1 enzyme-inhibitor complex involving porcine pancreatic elastase has been examined by X-ray crystallography and shown to result from serine acylation and sulfinate departure from the beta-lactam C-4.

The efficiency of C-4 substituents in activating the beta-lactam scaffold towards serine proteases and hydroxide ion.,Mulchande J, Martins L, Moreira R, Archer M, Oliveira TF, Iley J Org Biomol Chem. 2007 Aug 21;5(16):2617-26. PMID:18019537<ref>PMID:18019537</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 2v35" style="background-color:#fffaf0;"></div>

==See Also==
*[[Elastase 3D structures|Elastase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Archer M]]
[[Category: Iley J]]
[[Category: Martins L]]
[[Category: Moreira R]]
[[Category: Mulchande J]]
[[Category: Oliveira TF]]