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< | ==Structure of cytochrome P450 EryK in complex with inhibitor ketoconazole (KC)== | ||
<StructureSection load='2jjp' size='340' side='right'caption='[[2jjp]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2jjp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharopolyspora_erythraea Saccharopolyspora erythraea]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JJP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JJP FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=KLN:1-ACETYL-4-(4-{[(2S,4R)-2-(2,4-DICHLOROPHENYL)-2-(1H-IMIDAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL]METHOXY}PHENYL)PIPERAZINE'>KLN</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=2jjp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jjp OCA], [https://pdbe.org/2jjp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jjp RCSB], [https://www.ebi.ac.uk/pdbsum/2jjp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jjp ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ERYK_SACEN ERYK_SACEN] | |||
== 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/jj/2jjp_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/main_output.php?pdb_ID=2jjp 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> | ||
<div class="pdbe-citations 2jjp" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Saccharopolyspora erythraea]] | [[Category: Saccharopolyspora erythraea]] | ||
[[Category: Kendrew | [[Category: Kendrew SG]] | ||
[[Category: Miele | [[Category: Miele AE]] | ||
[[Category: Savino | [[Category: Savino C]] | ||
[[Category: Sciara | [[Category: Sciara G]] | ||
[[Category: Vallone | [[Category: Vallone B]] | ||
Latest revision as of 17:51, 13 December 2023
Structure of cytochrome P450 EryK in complex with inhibitor ketoconazole (KC)Structure of cytochrome P450 EryK in complex with inhibitor ketoconazole (KC)
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 PubMedEryK 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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