Gene - combatTB X

cyp51

Type: protein_coding
Name: cyp51
Locus Name: Rv0764c
Product: Cytochrome P450 51 Cyp51 (CYPL1) (P450-L1A1) (sterol 14-alpha demethylase) (lanosterol 14-alpha demethylase) (P450-14DM)
Functional Category: Intermediary metabolism and respiration
Location: 856682..858037 (- strand)
Gene Length: 1355 bp
Nucleotides: ATGAGCGCTGTTGCACTACCCCGGGTTTCGGGTGGCCACGACGAACACGGCCACCTCGAGGAGTTCCGCACCGATCCGATCGGGCTGATGCAACGGGTCCGCGACGAATGCGGAGACGTCGGTACCTTCCAGCTGGCCGGGAAGCAGGTCGTGCTGCTGTCCGGCTCGCACGCCAACGAATTCTTCTTCCGGGCGGGCGACGACGACCTGGACCAGGCCAAGGCATACCCGTTCATGACGCCGATCTTCGGCGAGGGCGTGGTGTTCGACGCCAGCCCGGAACGGCGTAAAGAGATGCTGCACAATGCCGCGCTACGCGGCGAGCAGATGAAGGGCCACGCTGCCACCATCGAAGATCAAGTCCGACGGATGATCGCCGACTGGGGTGAGGCCGGCGAGATCGATCTGCTGGACTTCTTCGCCGAGCTGACCATCTACACCTCCTCGGCCTGCCTGATCGGCAAGAAGTTCCGCGACCAGCTCGACGGGCGATTCGCCAAGCTCTATCACGAGTTGGAGCGCGGCACCGACCCACTAGCCTACGTCGACCCGTATCTGCCGATCGAGAGCTTCCGTCGCCGCGACGAAGCCCGCAATGGTCTGGTGGCACTGGTTGCGGACATCATGAACGGCCGGATCGCCAACCCACCCACCGACAAGAGCGACCGTGACATGCTCGACGTGCTCATCGCCGTCAAGGCTGAGACCGGCACTCCCCGGTTCTCGGCCGACGAGATCACCGGCATGTTCATCTCGATGATGTTCGCCGGCCATCACACCAGCTCGGGTACGGCTTCGTGGACGCTGATCGAGTTGATGCGCCATCGCGACGCCTACGCGGCCGTGATCGACGAACTCGACGAGCTGTACGGCGACGGCCGATCGGTGAGTTTCCATGCGCTGCGCCAGATTCCGCAGCTGGAAAACGTGCTGAAAGAGACGCTGCGCCTGCACCCTCCGCTGATCATCCTCATGCGAGTGGCCAAGGGCGAGTTCGAGGTGCAAGGCCACCGGATTCATGAGGGCGATCTGGTGGCGGCCTCCCCGGCGATCTCCAACCGGATCCCCGAAGACTTCCCCGATCCCCACGACTTCGTGCCAGCACGATACGAGCAGCCGCGCCAGGAAGATCTGCTCAACCGCTGGACGTGGATTCCGTTCGGCGCCGGCCGGCATCGTTGCGTGGGGGCGGCGTTCGCCATCATGCAGATCAAAGCGATCTTCTCGGTGTTGTTGCGCGAGTATGAGTTTGAGATGGCGCAACCGCCAGAAAGCTATCGTAACGACCATTCGAAGATGGTGGTGCAGTTGGCCCAGCCCGCTTGCGTGCGCTACCGCCGGCGAACGGGAGTTTA
Drug Resistance: Check for drug resistance association at TBDREAMDB
Mutations: Check for mutants available at TARGET

Function

Its precise biological substrate is not known. Catalyzes C14-demethylation of lanosterol, 24,25-dihydrolanosterol and obtusifoliol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol. {ECO:0000269|PubMed:10430874, ECO:0000269|PubMed:9756611}.

Family

Cytochrome P450 family

GO

heme binding GO:0020037 molecular_function
iron ion binding GO:0005506 molecular_function
cytosol GO:0005829 cellular_component
sterol 14-demethylase activity GO:0008398 molecular_function
oxidation-reduction process GO:0055114 biological_process
sterol biosynthetic process GO:0016126 biological_process
sterol metabolic process GO:0016125 biological_process

InterPro

UniProt: P9WPP9
GenBank: Rv0764c
EnsemblBacteria: Rv0764c
Mycobrowser: Rv0764c

PDB IDs:

Summary

Name: Lanosterol 14-alpha demethylase (EC 1.14.14.154) (CYPLI) (Cytochrome P450 51) (Cytochrome P450-14DM) (Cytochrome P450-LIA1) (Sterol 14-alpha demethylase)
Family: Cytochrome P450 family
Protein Sequence: MSAVALPRVSGGHDEHGHLEEFRTDPIGLMQRVRDECGDVGTFQLAGKQVVLLSGSHANEFFFRAGDDDLDQAKAYPFMTPIFGEGVVFDASPERRKEMLHNAALRGEQMKGHAATIEDQVRRMIADWGEAGEIDLLDFFAELTIYTSSACLIGKKFRDQLDGRFAKLYHELERGTDPLAYVDPYLPIESFRRRDEARNGLVALVADIMNGRIANPPTDKSDRDMLDVLIAVKAETGTPRFSADEITGMFISMMFAGHHTSSGTASWTLIELMRHRDAYAAVIDELDELYGDGRSVSFHALRQIPQLENVLKETLRLHPPLIILMRVAKGEFEVQGHRIHEGDLVAASPAISNRIPEDFPDPHDFVPARYEQPRQEDLLNRWTWIPFGAGRHRCVGAAFAIMQIKAIFSVLLREYEFEMAQPPESYRNDHSKMVVQLAQPACVRYRRRTGV
Mass: 50,878 Da
Length: 451 Aa

Rv0764c doesn't seem to be a targeted by any drug.

Rv0764c doesn't seem to be involved in any pathway.

Trypanosoma cruzi CYP51 inhibitor derived from a Mycobacterium tuberculosis screen hit.: PLoS Negl Trop Dis. 2009;3(2):e372. doi: 10.1371/journal.pntd.0000372. Epub 2009 Feb 3.
X-ray structure of 4,4'-dihydroxybenzophenone mimicking sterol substrate in the active site of sterol 14alpha-demethylase (CYP51).: J Biol Chem. 2008 May 30;283(22):15152-9. doi: 10.1074/jbc.M801145200. Epub 2008 Mar 26.
Small-molecule scaffolds for CYP51 inhibitors identified by high-throughput screening and defined by X-ray crystallography.: Antimicrob Agents Chemother. 2007 Nov;51(11):3915-23. doi: 10.1128/AAC.00311-07. Epub 2007 Sep 10.
Estriol bound and ligand-free structures of sterol 14alpha-demethylase.: Structure. 2004 Nov;12(11):1937-45. doi: 10.1016/j.str.2004.08.009.
Crystal structure of cytochrome P450 14alpha -sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors.: Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3068-73. doi: 10.1073/pnas.061562898.
Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry.: Mol Cell Proteomics. 2011 Dec;10(12):M111.011627. doi: 10.1074/mcp.M111.011445. Epub 2011 Oct 3.
Structural requirements for substrate recognition of Mycobacterium tuberculosis 14 alpha-demethylase: implications for sterol biosynthesis.: J Lipid Res. 2001 Jan;42(1):128-36.
Characterization and catalytic properties of the sterol 14alpha-demethylase from Mycobacterium tuberculosis.: Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8937-42. doi: 10.1073/pnas.96.16.8937.
CYP51-like gene of Mycobacterium tuberculosis actually encodes a P450 similar to eukaryotic CYP51.: J Biochem. 1998 Oct;124(4):694-6. doi: 10.1093/oxfordjournals.jbchem.a022167.
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.: Nature. 1998 Jun 11;393(6685):537-44. doi: 10.1038/31159.