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4ipw

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Revision as of 10:24, 11 August 2016

Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121

Structural highlights

4ipw is a 1 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	4ict, 4ips, 4iq7, 4iq9
Gene:	cyp121, Rv2276, MT2336, MTCY339.34c ("Bacillus tuberculosis" (Zopf 1883) Klein 1884)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Fonvielle M, Le Du MH, Lequin O, Lecoq A, Jacquet M, Thai R, Dubois S, Grach G, Gondry M, Belin P. Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121: insights from biochemical studies and crystal structures. J Biol Chem. 2013 Apr 25. PMID:23620594 doi:10.1074/jbc.M112.443853

1 Structural highlights
2 Publication Abstract from PubMed
3 See Also
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ipw"

@@ Line 1: / Line 1: @@
 ==Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121==
 <StructureSection load='4ipw' size='340' side='right' caption='[[4ipw]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ipw]] 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=4IPW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IPW FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4ipw]] 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=4IPW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IPW FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1G7:(3S,6S)-3-(3,4-DIHYDROXYBENZYL)-6-(4-HYDROXYBENZYL)PIPERAZINE-2,5-DIONE'>1G7</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]], [[4ips|4ips]], [[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=4ipw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ipw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ipw RCSB], [http://www.ebi.ac.uk/pdbsum/4ipw 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=4ipw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ipw OCA], [http://pdbe.org/4ipw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ipw RCSB], [http://www.ebi.ac.uk/pdbsum/4ipw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ipw ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4ipw" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 23: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Mycobacterium tuberculosis]]
 [[Category: Belin, P]]
 [[Category: Dubois, S]]

4ipw

From Proteopedia

Revision as of 10:24, 11 August 2016

Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121

Structural highlights

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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