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1epn

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[[Image:1epn.jpg|left|200px]]<br /><applet load="1epn" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1epn, resolution 1.6&Aring;" />
 
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'''A STRUCTURAL COMPARISON OF 21 INHIBITOR COMPLEXES OF THE ASPARTIC PROTEINASE FROM ENDOTHIA PARASITICA'''<br />
 
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==Overview==
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==A STRUCTURAL COMPARISON OF 21 INHIBITOR COMPLEXES OF THE ASPARTIC PROTEINASE FROM ENDOTHIA PARASITICA==
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The 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.
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<StructureSection load='1epn' size='340' side='right'caption='[[1epn]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1epn]] is a 1 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=1EPN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EPN FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2ZS:N-(MORPHOLIN-4-YLCARBONYL)-L-PHENYLALANYL-N-[(1R,2S)-1-(CYCLOHEXYLMETHYL)-2-HYDROXY-3-(1-METHYLETHOXY)-3-OXOPROPYL]-S-METHYL-L-CYSTEINAMIDE'>2ZS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1epn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1epn OCA], [https://pdbe.org/1epn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1epn RCSB], [https://www.ebi.ac.uk/pdbsum/1epn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1epn ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CARP_CRYPA CARP_CRYPA]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ep/1epn_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1epn ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1EPN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=CH3:'>CH3</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EPN OCA].
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*[[Pepsin|Pepsin]]
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__TOC__
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==Reference==
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</StructureSection>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7703859 7703859]
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[[Category: Cryphonectria parasitica]]
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[[Category: Endothiapepsin]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Blundell TL]]
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[[Category: Blundell, T L.]]
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[[Category: Cooper JB]]
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[[Category: Cooper, J B.]]
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[[Category: Crawford M]]
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[[Category: Crawford, M.]]
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[[Category: CH3]]
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[[Category: SO4]]
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[[Category: hydrolase(acid proteinase)]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:30:13 2008''
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Current revision

A STRUCTURAL COMPARISON OF 21 INHIBITOR COMPLEXES OF THE ASPARTIC PROTEINASE FROM ENDOTHIA PARASITICA

PDB ID 1epn

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