2xc3

From Proteopedia

(Difference between revisions)

Current revision

X-ray structure of Mycobacterium tuberculosis cyp125 bound to the reverse type I inhibitor

Structural highlights

2xc3 is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.5Å
Ligands:	,
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:http://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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2xc3"

@@ Line 3: / Line 3: @@
 <StructureSection load='2xc3' size='340' side='right'caption='[[2xc3]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2xc3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XC3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2xc3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XC3 FirstGlance]. <br>
-</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=RT8:NALPHA-[(TRANS-4-METHYLCYCLOHEXYL)CARBONYL]-N-PYRIDIN-4-YL-D-TRYPTOPHANAMIDE'>RT8</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]] 1.5&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2x5w|2x5w]], [[2x5l|2x5l]]</div></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=RT8:NALPHA-[(TRANS-4-METHYLCYCLOHEXYL)CARBONYL]-N-PYRIDIN-4-YL-D-TRYPTOPHANAMIDE'>RT8</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=2xc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xc3 OCA], [https://pdbe.org/2xc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xc3 RCSB], [https://www.ebi.ac.uk/pdbsum/2xc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xc3 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/CP125_MYCTU 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.<ref>PMID:19846551</ref> <ref>PMID:20545858</ref>
+[https://www.uniprot.org/uniprot/CP125_MYCTU 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.<ref>PMID:19846551</ref> <ref>PMID:20545858</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 24: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Myctu]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Kells, P M]]
+[[Category: Kells PM]]
-[[Category: Montellano, P R.Ortiz de]]
+[[Category: Ortiz de Montellano PR]]
-[[Category: Ouellet, H]]
+[[Category: Ouellet H]]
-[[Category: Podust, L M]]
+[[Category: Podust LM]]
-[[Category: Metal-binding]]
-[[Category: Oxidoreductase]]

2xc3

From Proteopedia

Current revision

X-ray structure of Mycobacterium tuberculosis cyp125 bound to the reverse type I inhibitor

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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