2x5l: Difference between revisions

Revision as of 10:08, 4 August 2016

X-RAY STRUCTURE OF THE SUBSTRATE-FREE MYCOBACTERIUM TUBERCULOSIS CYTOCHROME P450 CYP125, ALTERNATIVE CRYSTAL FORM

Structural highlights

2x5l is a 1 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	HEM
Related:	2x5w, 2xc3, 2xn8
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CP125_MYCTU] Catalyzes the C-27 hydroxylation of cholest-4-en-3-one and cholesterol and subsequently oxidizes the alcohol of the former to the cholest-4-en-3-one-27-oic acid via the aldehyde intermediate. Not required to incorporate the cholesterol side-chain carbon atoms into cellular lipids.^[1] ^[2]

Publication Abstract from PubMed

Cytochrome P450 CYP125A1 of Mycobacteriumtuberculosis, a potential therapeutic target for tuberculosis in humans, initiates degradation of the aliphatic chain of host cholesterol and is essential for establishing M. tuberculosis infection in a mouse model of disease. We explored the interactions of CYP125A1 with a reverse type I inhibitor by X-ray structure analysis and UV-vis spectroscopy. Compound LP10 (alpha-[(4-methylcyclohexyl)carbonyl amino]-N-4-pyridinyl-1H-indole-3-propanamide), previously identified as a potent type II inhibitor of Trypanosomacruzi CYP51, shifts CYP125A1 to a water-coordinated low-spin state upon binding with low micromolar affinity. When LP10 is present in the active site, the crystal structure and spectral characteristics both demonstrate changes in lipophilic and electronic properties favoring coordination of the iron axial water ligand. These results provide an insight into the structural requirements for developing selective CYP125A1 inhibitors.

Reverse type I inhibitor of Mycobacteriumtuberculosis CYP125A1.,Ouellet H, Kells PM, Ortiz de Montellano PR, Podust LM Bioorg Med Chem Lett. 2011 Jan 1;21(1):332-7. Epub 2010 Nov 5. PMID:21109436^[3]

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

References

↑ Capyk JK, Kalscheuer R, Stewart GR, Liu J, Kwon H, Zhao R, Okamoto S, Jacobs WR Jr, Eltis LD, Mohn WW. Mycobacterial cytochrome p450 125 (cyp125) catalyzes the terminal hydroxylation of c27 steroids. J Biol Chem. 2009 Dec 18;284(51):35534-42. doi: 10.1074/jbc.M109.072132. Epub . PMID:19846551 doi:https://dx.doi.org/10.1074/jbc.M109.072132
↑ Ouellet H, Guan S, Johnston JB, Chow ED, Kells PM, Burlingame AL, Cox JS, Podust LM, de Montellano PR. Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest-4-en-3-one. Mol Microbiol. 2010 Aug;77(3):730-42. Epub 2010 Jun 10. PMID:20545858 doi:10.1111/j.1365-2958.2010.07243.x
↑ Ouellet H, Kells PM, Ortiz de Montellano PR, Podust LM. Reverse type I inhibitor of Mycobacteriumtuberculosis CYP125A1. Bioorg Med Chem Lett. 2011 Jan 1;21(1):332-7. Epub 2010 Nov 5. PMID:21109436 doi:10.1016/j.bmcl.2010.11.007

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Capyk JK, Kalscheuer R, Stewart GR, Liu J, Kwon H, Zhao R, Okamoto S, Jacobs WR Jr, Eltis LD, Mohn WW. Mycobacterial cytochrome p450 125 (cyp125) catalyzes the terminal hydroxylation of c27 steroids. J Biol Chem. 2009 Dec 18;284(51):35534-42. doi: 10.1074/jbc.M109.072132. Epub . PMID:19846551 doi:https://dx.doi.org/10.1074/jbc.M109.072132

[2] Ouellet H, Guan S, Johnston JB, Chow ED, Kells PM, Burlingame AL, Cox JS, Podust LM, de Montellano PR. Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest-4-en-3-one. Mol Microbiol. 2010 Aug;77(3):730-42. Epub 2010 Jun 10. PMID:20545858 doi:10.1111/j.1365-2958.2010.07243.x

[3] Ouellet H, Kells PM, Ortiz de Montellano PR, Podust LM. Reverse type I inhibitor of Mycobacteriumtuberculosis CYP125A1. Bioorg Med Chem Lett. 2011 Jan 1;21(1):332-7. Epub 2010 Nov 5. PMID:21109436 doi:10.1016/j.bmcl.2010.11.007

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
 ==X-RAY STRUCTURE OF THE SUBSTRATE-FREE MYCOBACTERIUM TUBERCULOSIS CYTOCHROME P450 CYP125, ALTERNATIVE CRYSTAL FORM==
 <StructureSection load='2x5l' size='340' side='right' caption='[[2x5l]], [[Resolution|resolution]] 1.48&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2x5l]] 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=2X5L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X5L FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2x5l]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X5L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X5L FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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">[[2x5w|2x5w]], [[2xc3|2xc3]], [[2xn8|2xn8]]</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=2x5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x5l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2x5l RCSB], [http://www.ebi.ac.uk/pdbsum/2x5l 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=2x5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x5l OCA], [http://pdbe.org/2x5l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2x5l RCSB], [http://www.ebi.ac.uk/pdbsum/2x5l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2x5l ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2x5l" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Mycobacterium tuberculosis]]
+[[Category: Myctu]]
 [[Category: Kells, P M]]
 [[Category: Montellano, P R.Ortiz De]]

2x5l: Difference between revisions

Revision as of 10:08, 4 August 2016

X-RAY STRUCTURE OF THE SUBSTRATE-FREE MYCOBACTERIUM TUBERCULOSIS CYTOCHROME P450 CYP125, ALTERNATIVE CRYSTAL FORM

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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