2v35: Difference between revisions
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< | ==Porcine Pancreatic Elastase in complex with inhibitor JM54== | ||
<StructureSection load='2v35' size='340' side='right'caption='[[2v35]], [[Resolution|resolution]] 1.67Å' scene=''> | |||
You may | == 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]] 1.67Å</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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2v35" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Elastase 3D structures|Elastase 3D structures]] | |||
== | == References == | ||
<references/> | |||
__TOC__ | |||
[[Category: | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
[[Category: Archer | [[Category: Archer M]] | ||
[[Category: Iley | [[Category: Iley J]] | ||
[[Category: Martins | [[Category: Martins L]] | ||
[[Category: Moreira | [[Category: Moreira R]] | ||
[[Category: Mulchande | [[Category: Mulchande J]] | ||
[[Category: Oliveira | [[Category: Oliveira TF]] | ||
Latest revision as of 15:04, 13 December 2023
Porcine Pancreatic Elastase in complex with inhibitor JM54
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