4ips - Revision history

OCA at 11:10, 13 August 2026

2026-08-13T11:10:26Z

← Older revision		Revision as of 11:10, 13 August 2026
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/CP121_MYCTU CP121_MYCTU]		[https://www.uniprot.org/uniprot/CP121_MYCTU CP121_MYCTU]
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			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.

			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>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4ips" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]		*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 11:58, 1 March 2024

2024-03-01T11:58:50Z

← Older revision		Revision as of 11:58, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ips]] 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=4IPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IPS FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ips]] 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=4IPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IPS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1G4:(3S,6S)-3,6-BIS(4-HYDROXYBENZYL)PIPERAZIN-2-ONE'>1G4</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>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.2Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1G4:(3S,6S)-3,6-BIS(4-HYDROXYBENZYL)PIPERAZIN-2-ONE'>1G4</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>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ips FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ips OCA], [https://pdbe.org/4ips PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ips RCSB], [https://www.ebi.ac.uk/pdbsum/4ips PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ips ProSAT]</span></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=4ips FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ips OCA], [https://pdbe.org/4ips PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ips RCSB], [https://www.ebi.ac.uk/pdbsum/4ips PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ips ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/CP121_MYCTU CP121_MYCTU]		[https://www.uniprot.org/uniprot/CP121_MYCTU CP121_MYCTU]
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	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.

	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>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4ips" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]		*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 21:02, 16 November 2022

2022-11-16T21:02:32Z

← Older revision		Revision as of 21:02, 16 November 2022
Line 1:		Line 1:

	==Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121==		==Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121==
	<StructureSection load='4ips' size='340' side='right' caption='[[4ips]], [[Resolution\|resolution]] 1.20Å' scene=''>		<StructureSection load='4ips' size='340' side='right'caption='[[4ips]], [[Resolution\|resolution]] 1.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ips]] 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=4IPS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4IPS FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ips]] 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=4IPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IPS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1G4:(3S,6S)-3,6-BIS(4-HYDROXYBENZYL)PIPERAZIN-2-ONE'>1G4</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>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1G4:(3S,6S)-3,6-BIS(4-HYDROXYBENZYL)PIPERAZIN-2-ONE'>1G4</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>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ict\|4ict]], [[4ipw\|4ipw]], [[4iq7\|4iq7]], [[4iq9\|4iq9]]</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=4ips FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ips OCA], [https://pdbe.org/4ips PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ips RCSB], [https://www.ebi.ac.uk/pdbsum/4ips PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ips ProSAT]</span></td></tr>
	<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>
	<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=4ips FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ips OCA], [~~http~~://pdbe.org/4ips PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ips RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ips PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ips ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/CP121_MYCTU CP121_MYCTU]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 20:

	==See Also==		==See Also==
	*[[Cytochrome P450\|Cytochrome P450]]		*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Belin, P]]		[[Category: Large Structures]]
	[[Category: Dubois, S]]		[[Category: Mycobacterium tuberculosis]]
	[[Category: Fonvielle, M]]		[[Category: Belin P]]
	[[Category: Gondry, M]]		[[Category: Dubois S]]
	[[Category: Grach, G]]		[[Category: Fonvielle M]]
	[[Category: Jacquet, M]]		[[Category: Gondry M]]
	[[Category: LeDu~~, M H~~]]		[[Category: Grach G]]
	[[Category: Lecoq, A]]		[[Category: Jacquet M]]
	[[Category: Lequin, O]]		[[Category: LeDu MH]]
	[[Category: Thai, R]]		[[Category: Lecoq A]]
	~~[[Category: Cyclo-dipeptide]]~~		[[Category: Lequin O]]
	~~[[Category: Oxidoreductase]]~~		[[Category: Thai R]]
	~~[[Category: Oxydase]]~~
	~~[[Category: P450 fold]]~~
	~~[[Category: Protein-ligand complex~~]]

OCA at 11:21, 11 August 2016

2016-08-11T11:21:30Z

← Older revision		Revision as of 11:21, 11 August 2016
Line 1:		Line 1:

	==Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121==		==Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121==
	<StructureSection load='4ips' size='340' side='right' caption='[[4ips]], [[Resolution\|resolution]] 1.20Å' scene=''>		<StructureSection load='4ips' size='340' side='right' caption='[[4ips]], [[Resolution\|resolution]] 1.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ips]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Mycobacterium_tuberculosis Mycobacterium~~ tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IPS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IPS FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ips]] 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=4IPS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IPS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1G4:(3S,6S)-3,6-BIS(4-HYDROXYBENZYL)PIPERAZIN-2-ONE'>1G4</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>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1G4:(3S,6S)-3,6-BIS(4-HYDROXYBENZYL)PIPERAZIN-2-ONE'>1G4</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>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ict\|4ict]], [[4ipw\|4ipw]], [[4iq7\|4iq7]], [[4iq9\|4iq9]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ict\|4ict]], [[4ipw\|4ipw]], [[4iq7\|4iq7]], [[4iq9\|4iq9]]</td></tr>
	<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 ~~Mycobacterium~~ tuberculosis])</td></tr>		<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>
	<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=4ips FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ips OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ips RCSB], [http://www.ebi.ac.uk/pdbsum/4ips PDBsum]</span></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=4ips FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ips OCA], [http://pdbe.org/4ips PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ips RCSB], [http://www.ebi.ac.uk/pdbsum/4ips PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ips ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 16:		Line 17:
	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 4ips" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 23:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Mycobacterium tuberculosis]]~~
	[[Category: Belin, P]]		[[Category: Belin, P]]
	[[Category: Dubois, S]]		[[Category: Dubois, S]]

OCA at 08:35, 20 January 2015

2015-01-20T08:35:48Z

← Older revision		Revision as of 08:35, 20 January 2015
Line 1:		Line 1:
	~~{{STRUCTURE_4ips\| PDB=4ips \| SCENE= }}~~		==Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121==
	===Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121===		<StructureSection load='4ips' size='340' side='right' caption='[[4ips]], [[Resolution\|resolution]] 1.20Å' scene=''>
	~~{{ABSTRACT_PUBMED_23620594}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4ips]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IPS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IPS FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1G4:(3S,6S)-3,6-BIS(4-HYDROXYBENZYL)PIPERAZIN-2-ONE'>1G4</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>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ict\|4ict]], [[4ipw\|4ipw]], [[4iq7\|4iq7]], [[4iq9\|4iq9]]</td></tr>
			<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 Mycobacterium tuberculosis])</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=4ips FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ips OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ips RCSB], [http://www.ebi.ac.uk/pdbsum/4ips PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			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.

	~~==About this Structure==~~		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>
	~~[[4ips]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis~~ Mycobacterium tuberculosis~~]. Full crystallographic information is available~~ from ~~[http://oca~~.~~weizmann~~.ac.~~il/oca-bin~~/~~ocashort?id=4IPS OCA].~~

	==~~Reference~~==		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~<ref group~~=~~"xtra">PMID:023620594</ref>~~<references ~~group="xtra"~~/><~~references~~/>		</div>

			==See Also==
			*[[Cytochrome P450\|Cytochrome P450]]
			== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Mycobacterium tuberculosis]]		[[Category: Mycobacterium tuberculosis]]
	[[Category: Belin, P.]]		[[Category: Belin, P]]
	[[Category: Dubois, S.]]		[[Category: Dubois, S]]
	[[Category: Fonvielle, M.]]		[[Category: Fonvielle, M]]
	[[Category: Gondry, M.]]		[[Category: Gondry, M]]
	[[Category: Grach, G.]]		[[Category: Grach, G]]
	[[Category: Jacquet, M.]]		[[Category: Jacquet, M]]
	[[Category: LeDu, M H.]]		[[Category: LeDu, M H]]
	[[Category: Lecoq, A.]]		[[Category: Lecoq, A]]
	[[Category: Lequin, O.]]		[[Category: Lequin, O]]
	[[Category: Thai, R.]]		[[Category: Thai, R]]
	[[Category: Cyclo-dipeptide]]		[[Category: Cyclo-dipeptide]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]

OCA at 14:27, 3 July 2013

2013-07-03T14:27:53Z

← Older revision		Revision as of 14:27, 3 July 2013
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	==About this Structure==		==About this Structure==
	[[4ips]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IPS OCA].		[[4ips]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IPS OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:023620594</ref><references group="xtra"/><references/>		<ref group="xtra">PMID:023620594</ref><references group="xtra"/><references/>
			[[Category: Mycobacterium tuberculosis]]
	[[Category: Belin, P.]]		[[Category: Belin, P.]]
	[[Category: Dubois, S.]]		[[Category: Dubois, S.]]

OCA at 12:13, 3 July 2013

2013-07-03T12:13:54Z

← Older revision		Revision as of 12:13, 3 July 2013
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	==About this Structure==		==About this Structure==
	[[4ips]] is a 1 chain structure ~~with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IPS OCA].		[[4ips]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IPS OCA].
	~~[[Category~~: ~~Mycobacterium tuberculosis]]~~
			==Reference==
			<ref group="xtra">PMID:023620594</ref><references group="xtra"/><references/>
	[[Category: Belin, P.]]		[[Category: Belin, P.]]
	[[Category: Dubois, S.]]		[[Category: Dubois, S.]]

OCA at 06:46, 8 May 2013

2013-05-08T06:46:27Z

← Older revision		Revision as of 06:46, 8 May 2013
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	{{STRUCTURE_4ips\| PDB=4ips \| SCENE= }}		{{STRUCTURE_4ips\| PDB=4ips \| SCENE= }}
	===Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121===		===Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121===
			{{ABSTRACT_PUBMED_23620594}}

	==About this Structure==		==About this Structure==

OCA at 07:52, 2 May 2013

2013-05-02T07:52:36Z

← Older revision		Revision as of 07:52, 2 May 2013
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	~~'''Unreleased structure'''~~		{{STRUCTURE_4ips\| PDB=4ips \| SCENE= }}
			===Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121===

	~~The entry~~ 4ips is ~~ON HOLD until Paper Publication~~		==About this Structure==
			[[4ips]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IPS OCA].
	~~Authors~~: ~~Fonvielle~~, M., ~~LeDu~~, M.H., ~~Lequin, O~~., ~~Lecoq, A~~., Jacquet, M., ~~Thai, R~~., ~~Dubois, S~~., ~~Grach, G~~., ~~Gondry, M., Belin, P~~.		[[Category: Mycobacterium tuberculosis]]
			[[Category: Belin, P.]]
	~~Description~~: ~~Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome~~ P450 ~~CYP121~~		[[Category: Dubois, S.]]
			[[Category: Fonvielle, M.]]
			[[Category: Gondry, M.]]
			[[Category: Grach, G.]]
			[[Category: Jacquet, M.]]
			[[Category: LeDu, M H.]]
			[[Category: Lecoq, A.]]
			[[Category: Lequin, O.]]
			[[Category: Thai, R.]]
			[[Category: Cyclo-dipeptide]]
			[[Category: Oxidoreductase]]
			[[Category: Oxydase]]
			[[Category: P450 fold]]
			[[Category: Protein-ligand complex]]

OCA at 12:02, 30 January 2013

2013-01-30T12:02:55Z

← Older revision		Revision as of 12:02, 30 January 2013
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4ips is ON HOLD		The entry 4ips is ON HOLD until Paper Publication

	Authors: Fonvielle, M., ~~Le Du~~, M-H, Lequin, O., Lecoq, A., Jacquet, M., Thai , R., Dubois, S., Grach, G., Gondry, M., Belin, P.		Authors: Fonvielle, M., LeDu, M.H., Lequin, O., Lecoq, A., Jacquet, M., Thai, R., Dubois, S., Grach, G., Gondry, M., Belin, P.

	Description: Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121		Description: Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121