2v35: Difference between revisions
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[[Image: | ==PORCINE PANCREATIC ELASTASE IN COMPLEX WITH INHIBITOR JM54== | ||
<StructureSection load='2v35' size='340' side='right' caption='[[2v35]], [[Resolution|resolution]] 1.67Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2v35]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2V35 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1b0e|1b0e]], [[1bma|1bma]], [[1btu|1btu]], [[1c1m|1c1m]], [[1e34|1e34]], [[1e35|1e35]], [[1e36|1e36]], [[1e37|1e37]], [[1e38|1e38]], [[1eai|1eai]], [[1eas|1eas]], [[1eat|1eat]], [[1eau|1eau]], [[1ela|1ela]], [[1elb|1elb]], [[1elc|1elc]], [[1eld|1eld]], [[1ele|1ele]], [[1elf|1elf]], [[1elg|1elg]], [[1esa|1esa]], [[1esb|1esb]], [[1est|1est]], [[1fle|1fle]], [[1fzz|1fzz]], [[1gvk|1gvk]], [[1gwa|1gwa]], [[1h9l|1h9l]], [[1hax|1hax]], [[1hay|1hay]], [[1haz|1haz]], [[1hb0|1hb0]], [[1hv7|1hv7]], [[1inc|1inc]], [[1jim|1jim]], [[1l0z|1l0z]], [[1l1g|1l1g]], [[1lka|1lka]], [[1lkb|1lkb]], [[1lvy|1lvy]], [[1mcv|1mcv]], [[1mmj|1mmj]], [[1nes|1nes]], [[1okx|1okx]], [[1qgf|1qgf]], [[1qix|1qix]], [[1qnj|1qnj]], [[1qr3|1qr3]], [[1uo6|1uo6]], [[1uvo|1uvo]], [[1uvp|1uvp]], [[2a7c|2a7c]], [[2a7j|2a7j]], [[2blo|2blo]], [[2blq|2blq]], [[2cv3|2cv3]], [[2d26|2d26]], [[2de8|2de8]], [[2de9|2de9]], [[2est|2est]], [[2h1u|2h1u]], [[2v0b|2v0b]], [[3est|3est]], [[4est|4est]], [[5est|5est]], [[6est|6est]], [[7est|7est]], [[8est|8est]], [[9est|9est]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pancreatic_elastase Pancreatic elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.36 3.4.21.36] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2v35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v35 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2v35 RCSB], [http://www.ebi.ac.uk/pdbsum/2v35 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/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/chain_selection.php?pdb_ID=2ata 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> | |||
==See Also== | ==See Also== | ||
*[[Elastase|Elastase]] | *[[Elastase|Elastase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Pancreatic elastase]] | [[Category: Pancreatic elastase]] | ||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
