2xfh
From Proteopedia
(Difference between revisions)
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| - | + | ==Structure of cytochrome P450 EryK cocrystallized with inhibitor clotrimazole.== | |
| - | + | <StructureSection load='2xfh' size='340' side='right' caption='[[2xfh]], [[Resolution|resolution]] 1.90Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[2xfh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"actinomyces_erythreus"_(sic)_waksman_1923 "actinomyces erythreus" (sic) waksman 1923]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2vrv 2vrv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XFH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XFH FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL6:1-[(2-CHLOROPHENYL)(DIPHENYL)METHYL]-1H-IMIDAZOLE'>CL6</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wio|2wio]], [[2jjn|2jjn]], [[2vrv|2vrv]], [[2jjp|2jjp]], [[2jjo|2jjo]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xfh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xfh RCSB], [http://www.ebi.ac.uk/pdbsum/2xfh 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/xf/2xfh_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 == | ||
| + | EryK is a bacterial cytochrome P450 that catalyzes the last hydroxylation occurring during the biosynthetic pathway of erythromycin A in Streptomyces erythraeus. We report the crystal structures of EryK in complex with two widely used azole inhibitors: ketoconazole and clotrimazole. Both these ligands use their imidazole moiety to coordinate the heme iron of P450s. Nevertheless, because of the different chemical and structural properties of their N1-substituent group, ketoconazole and clotrimazole trap EryK, respectively, in a closed and in an open conformation that resemble the two structures previously described for the ligand-free EryK. Indeed ligands induce a distortion of the internal helix I that affects the accessibility of the binding pocket by regulating the kink of the external helix G via a network of interactions that involves helix F. The data presented thus constitute an example of how a cytochrome P450 may be selectively trapped in different conformational states by inhibitors. | ||
| - | + | Azole drugs trap cytochrome P450 EryK in alternative conformational states.,Montemiglio LC, Gianni S, Vallone B, Savino C Biochemistry. 2010 Sep 16. PMID:20845962<ref>PMID:20845962</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| - | [[Category: Gianni, S | + | == References == |
| - | [[Category: Montemiglio, L C | + | <references/> |
| - | [[Category: Savino, C | + | __TOC__ |
| - | [[Category: Vallone, B | + | </StructureSection> |
| + | [[Category: Gianni, S]] | ||
| + | [[Category: Montemiglio, L C]] | ||
| + | [[Category: Savino, C]] | ||
| + | [[Category: Vallone, B]] | ||
[[Category: Erythromycin a biosynthesis]] | [[Category: Erythromycin a biosynthesis]] | ||
[[Category: Monoxygenase]] | [[Category: Monoxygenase]] | ||
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
Revision as of 17:11, 21 December 2014
Structure of cytochrome P450 EryK cocrystallized with inhibitor clotrimazole.
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