1e34: Difference between revisions
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[[Image: | ==PORCINE PANCREATIC ELASTASE COMPLEXED WITH (3S, 4S)N-PARA-TOLUENESULPHONYL-3-ETHYL-4-(CARBOXYLIC ACID) PYRROLIDIN-2-ONE SOAKED IN PH 9 BUFFER FOR ONE MINUTE== | ||
<StructureSection load='1e34' size='340' side='right' caption='[[1e34]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1e34]] 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=1E34 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1E34 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TPX:(2S,3S)-3-FORMYL-2-({[(4-METHYLPHENYL)SULFONYL]AMINO}METHYL)PENTANOIC+ACID'>TPX</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3est|3est]], [[1qgf|1qgf]], [[1e35|1e35]], [[1e36|1e36]], [[1e37|1e37]], [[1e38|1e38]], [[1est|1est]], [[2est|2est]], [[4est|4est]], [[5est|5est]], [[6est|6est]], [[7est|7est]], [[8est|8est]], [[9est|9est]], [[1inc|1inc]], [[1jim|1jim]], [[1ela|1ela]], [[1elb|1elb]], [[1elc|1elc]], [[1eld|1eld]], [[1ele|1ele]], [[1elf|1elf]], [[1elg|1elg]], [[1esa|1esa]], [[1esb|1esb]], [[1eai|1eai]], [[1eas|1eas]], [[1eat|1eat]], [[1eau|1eau]], [[1bma|1bma]], [[1lvy|1lvy]], [[1nes|1nes]], [[1b0e|1b0e]], [[1btu|1btu]]</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=1e34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e34 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1e34 RCSB], [http://www.ebi.ac.uk/pdbsum/1e34 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/e3/1e34_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 == | |||
beta-Lactams inhibit a range of enzymes via acylation of nucleophilic serine residues. Certain gamma-lactam analogues of monocyclic beta-lactams have also been shown to be reversible inhibitors of porcine pancreatic elastase (PPE), forming acyl-enzyme complexes that are stable with respect to hydrolysis. Crystallographic analysis at pH 5 of an acyl-enzyme complex formed with PPE and one of these inhibitors revealed the ester carbonyl located in the oxyanion hole in a similar conformation to that observed in the structure of a complex formed between a heptapeptide (beta-casomorphin-7) and PPE. Only weak electron density was observed for the His-57 side chain in its 'native' conformation. Instead, the His-57 side chain predominantly adopted a conformation rotated approx. 90 degrees from its normal position. PPE-gamma-lactam crystals were subjected to 'pH-jumps' by placing the crystals in a buffer of increased pH prior to freezing for data collection. The results indicate that the conformation of the gamma-lactam-derived acyl-enzyme species in the PPE active site is dependent on pH, a result having implications for the analysis of other serine protease-inhibitor structures at non-catalytic pH values. The results help to define the stereoelectronic relationship between the ester of the acyl-enzyme complex, the side chain of His-57 and the incoming nucleophile during the reversible (de)acylation steps, implying it is closely analogous to the hydrolytic deacylation step during catalytic peptide hydrolysis. | |||
'pH-jump' crystallographic analyses of gamma-lactam-porcine pancreatic elastase complexes.,Wright PA, Wilmouth RC, Clifton IJ, Schofield CJ Biochem J. 2000 Oct 15;351 Pt 2:335-40. PMID:11023818<ref>PMID:11023818</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]] | ||
Revision as of 13:53, 10 September 2014
PORCINE PANCREATIC ELASTASE COMPLEXED WITH (3S, 4S)N-PARA-TOLUENESULPHONYL-3-ETHYL-4-(CARBOXYLIC ACID) PYRROLIDIN-2-ONE SOAKED IN PH 9 BUFFER FOR ONE MINUTEPORCINE PANCREATIC ELASTASE COMPLEXED WITH (3S, 4S)N-PARA-TOLUENESULPHONYL-3-ETHYL-4-(CARBOXYLIC ACID) PYRROLIDIN-2-ONE SOAKED IN PH 9 BUFFER FOR ONE MINUTE
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedbeta-Lactams inhibit a range of enzymes via acylation of nucleophilic serine residues. Certain gamma-lactam analogues of monocyclic beta-lactams have also been shown to be reversible inhibitors of porcine pancreatic elastase (PPE), forming acyl-enzyme complexes that are stable with respect to hydrolysis. Crystallographic analysis at pH 5 of an acyl-enzyme complex formed with PPE and one of these inhibitors revealed the ester carbonyl located in the oxyanion hole in a similar conformation to that observed in the structure of a complex formed between a heptapeptide (beta-casomorphin-7) and PPE. Only weak electron density was observed for the His-57 side chain in its 'native' conformation. Instead, the His-57 side chain predominantly adopted a conformation rotated approx. 90 degrees from its normal position. PPE-gamma-lactam crystals were subjected to 'pH-jumps' by placing the crystals in a buffer of increased pH prior to freezing for data collection. The results indicate that the conformation of the gamma-lactam-derived acyl-enzyme species in the PPE active site is dependent on pH, a result having implications for the analysis of other serine protease-inhibitor structures at non-catalytic pH values. The results help to define the stereoelectronic relationship between the ester of the acyl-enzyme complex, the side chain of His-57 and the incoming nucleophile during the reversible (de)acylation steps, implying it is closely analogous to the hydrolytic deacylation step during catalytic peptide hydrolysis. 'pH-jump' crystallographic analyses of gamma-lactam-porcine pancreatic elastase complexes.,Wright PA, Wilmouth RC, Clifton IJ, Schofield CJ Biochem J. 2000 Oct 15;351 Pt 2:335-40. PMID:11023818[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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