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==A STRUCTURAL COMPARISON OF 21 INHIBITOR COMPLEXES OF THE ASPARTIC PROTEINASE FROM ENDOTHIA PARASITICA== | ==A STRUCTURAL COMPARISON OF 21 INHIBITOR COMPLEXES OF THE ASPARTIC PROTEINASE FROM ENDOTHIA PARASITICA== | ||
<StructureSection load='1epm' size='340' side='right' caption='[[1epm]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='1epm' size='340' side='right'caption='[[1epm]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1epm]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1epm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EPM FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> | ||
<tr><td class="sblockLbl"><b>[[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PSA:3-HYDROXY-4-AMINO-5-PHENYLPENTANOIC+ACID'>PSA</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=1epm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1epm OCA], [https://pdbe.org/1epm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1epm RCSB], [https://www.ebi.ac.uk/pdbsum/1epm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1epm ProSAT]</span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </table> | ||
<table> | == Function == | ||
[https://www.uniprot.org/uniprot/CARP_CRYPA CARP_CRYPA] | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ep/1epm_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ep/1epm_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=1epm ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 26: | Line 28: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 1epm" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Pepsin|Pepsin]] | *[[Pepsin|Pepsin]] | ||
*[[Proteinase 3D structures|Proteinase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 34: | Line 38: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Cryphonectria parasitica]] | [[Category: Cryphonectria parasitica]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Blundell | [[Category: Blundell TL]] | ||
[[Category: Cooper | [[Category: Cooper JB]] | ||
[[Category: Crawford | [[Category: Crawford M]] | ||
[[Category: Strop | [[Category: Strop P]] | ||
Latest revision as of 11:25, 6 November 2024
A STRUCTURAL COMPARISON OF 21 INHIBITOR COMPLEXES OF THE ASPARTIC PROTEINASE FROM ENDOTHIA PARASITICAA STRUCTURAL COMPARISON OF 21 INHIBITOR COMPLEXES OF THE ASPARTIC PROTEINASE FROM ENDOTHIA PARASITICA
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe aspartic proteinases are an important family of enzymes associated with several pathological conditions such as hypertension (renin), gastric ulcers (pepsin), neoplastic disease (cathepsins D and E), and AIDS (HIV proteinase). Studies of inhibitor binding are therefore of great importance for design of novel inhibitors for potential therapeutic applications. Numerous X-ray analyses have shown that transition-state isostere inhibitors of aspartic proteinases bind in similar extended conformations in the active-site cleft of the target enzyme. Upon comparison of 21 endothiapepsin inhibitor complexes, the hydrogen bond lengths were found to be shortest where the isostere (P1-P'1) interacts with the enzyme's catalytic aspartate pair. Hydrogen bonds with good geometry also occur at P'2, and more so at P3, where a conserved water molecule is involved in the interactions. Weaker interactions also occur at P2, where the side-chain conformations of the inhibitors appear to be more variable than at the more tightly held positions. At P2 and, to a lesser extent, P3, the side-chain conformations depend intriguingly on interactions with spatially adjacent side chains, namely P'1 and P1, respectively. The tight binding at P1-P'1, P3, and P'2 is also reflected in the larger number of van der Waals contacts and the large decreases in solvent-accessible area at these positions, as well as their low temperature factors. Our analysis substantiates earlier proposals for the locations of protons in the transition-state complex. Aspartate 32 is probably ionized in the complexes, its charge being stabilized by 1, or sometimes 2, hydrogen bonds from the transition-state analogues at P1. The detailed comparison also indicates that the P1 and P2 residues of substrate in the ES complex may be strained by the extensive binding interactions at P3, P'1, and P'2 in a manner that would facilitate hydrolysis of the scissile peptide bond. A structural comparison of 21 inhibitor complexes of the aspartic proteinase from Endothia parasitica.,Bailey D, Cooper JB Protein Sci. 1994 Nov;3(11):2129-43. PMID:7703859[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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