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4iq9

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==Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121==
==Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121==
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<StructureSection load='4iq9' size='340' side='right' caption='[[4iq9]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
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<StructureSection load='4iq9' size='340' side='right'caption='[[4iq9]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4iq9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IQ9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IQ9 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4iq9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IQ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IQ9 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1GB:(3S,6S)-3-(4-HYDROXYBENZYL)-6-(1H-INDOL-3-YLMETHYL)PIPERAZINE-2,5-DIONE'>1GB</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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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]] 1.4&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ict|4ict]], [[4ipw|4ipw]], [[4ips|4ips]], [[4iq7|4iq7]]</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=1GB:(3S,6S)-3-(4-HYDROXYBENZYL)-6-(1H-INDOL-3-YLMETHYL)PIPERAZINE-2,5-DIONE'>1GB</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cyp121, Rv2276, MT2336, MTCY339.34c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=4iq9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iq9 OCA], [https://pdbe.org/4iq9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iq9 RCSB], [https://www.ebi.ac.uk/pdbsum/4iq9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iq9 ProSAT]</span></td></tr>
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<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=4iq9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iq9 OCA], [http://pdbe.org/4iq9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iq9 RCSB], [http://www.ebi.ac.uk/pdbsum/4iq9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iq9 ProSAT]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/CP121_MYCTU CP121_MYCTU]
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Cytochrome P450 CYP121 is essential for the viability of Mycobacterium tuberculosis. Studies in vitro show that it can use the cyclodipeptide cyclo(L-Tyr-L-Tyr) (cYY)6 as a substrate. We report an investigation of the substrate and reaction specificities of CYP121 involving analysis of the interaction between CYP121 and 14 cYY analogues with various modifications of the side chains or the diketopiperazine (DKP) ring. Spectral titration experiments show that CYP121 significantly bound only cyclodipeptides with a conserved DKP ring carrying two aryl side chains in L configuration. CYP121 did not efficiently or selectively transform any of the cYY analogues tested, indicating a high specificity for cYY. The molecular determinants of this specificity were inferred from both crystal structures of CYP121/analogue complexes solved at high resolution and solution NMR spectroscopy of the analogues. Bound cYY or its analogues all displayed a similar set of contacts with CYP121 residues Asn85, Phe168 and Trp182. The propensity of the cYY tyrosyl to point toward Arg386 was dependent on the presence of the DKP ring that limits the conformational freedom of the ligand. The correct positioning of the hydroxyl of this tyrosyl was essential for conversion of cYY. Thus, the specificity of CYP121 results from both a restricted binding specificity and a fine-tuned P450 substrate relationship. These results document the catalytic mechanism of CYP121 and improve our understanding of its function in vivo. This work contributes to progress towards the design of inhibitors of this essential protein of M. tuberculosis that could be used for antituberculosis therapy.
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Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121: insights from biochemical studies and crystal structures.,Fonvielle M, Le Du MH, Lequin O, Lecoq A, Jacquet M, Thai R, Dubois S, Grach G, Gondry M, Belin P J Biol Chem. 2013 Apr 25. PMID:23620594<ref>PMID:23620594</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4iq9" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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*[[Cytochrome P450|Cytochrome P450]]
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*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Belin, P]]
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[[Category: Large Structures]]
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[[Category: Dubois, S]]
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[[Category: Mycobacterium tuberculosis]]
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[[Category: Fonvielle, M]]
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[[Category: Belin P]]
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[[Category: Gondry, M]]
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[[Category: Dubois S]]
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[[Category: Grach, G]]
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[[Category: Fonvielle M]]
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[[Category: Jacquet, M]]
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[[Category: Gondry M]]
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[[Category: Lecoq, A]]
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[[Category: Grach G]]
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[[Category: Ledu, M H]]
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[[Category: Jacquet M]]
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[[Category: Lequin, O]]
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[[Category: Lecoq A]]
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[[Category: Thai, R]]
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[[Category: Ledu MH]]
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[[Category: Oxidase]]
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[[Category: Lequin O]]
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[[Category: Oxidoreductase]]
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[[Category: Thai R]]
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[[Category: P450 fold]]
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[[Category: Protein-ligand complex]]
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Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121

PDB ID 4iq9

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