TB Genome Annotation Portal

Rv0764c (cyp51)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: lanosterol 14-alpha demethylase
  • REFSEQ: cytochrome P450 sterol 14-alpha demethylase
  • PATRIC: Cytochrome P450 51
  • TUBERCULIST: Cytochrome P450 51 Cyp51 (CYPL1) (P450-L1A1) (sterol 14-alpha demethylase) (lanosterol 14-alpha demethylase) (P450-14DM)
  • NCBI: Cytochrome P450 51 Cyp51 (CYPL1) (P450-L1A1) (sterol 14-alpha demethylase) (lanosterol 14-alpha demethylase) (P450-14DM)
  • updated information (H37Rv4):
    • gene name: cyp51
    • function:
    • reference:
• Type: Not Target
• Start: 856682
• End: 858037
• Operon:


• Trans-membrane region:
  
• Role: IV.F - Cytochrome P450 enzymes
• GO terms:
  • GO:0070988 - demethylation (Uniprot)
  • GO:0055114 - oxidation-reduction process (Uniprot)
  • GO:0046872 - metal ion binding (Uniprot)
  • GO:0020037 - heme binding (Uniprot)
  • GO:0016705 - oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (Uniprot)
  • GO:0016491 - oxidoreductase activity (Uniprot)
  • GO:0016126 - sterol biosynthetic process (Uniprot)
  • GO:0016125 - sterol metabolic process (Uniprot)
  • GO:0008398 - sterol 14-demethylase activity (Uniprot)
  • GO:0008202 - steroid metabolic process (Uniprot)
  • GO:0006694 - steroid biosynthetic process (Uniprot)
  • GO:0006629 - lipid metabolic process (Uniprot)
  • GO:0005829 - cytosol (Uniprot)
  • GO:0005737 - cytoplasm (Uniprot)
  • GO:0005515 - protein binding (Uniprot)
  • GO:0005506 - iron ion binding (Uniprot)
  • GO:0004497 - monooxygenase activity (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
• Gene Expression Profile (Transcriptional Responses to Drugs; Boshoff et al, 2004)
• Gene Modules extracted from cluster analysis of 249 transcriptomic datasets using ICA
• Orthologs among selected mycobacteria
• Protein structure: 2w0b, 1u13, 1ea1, 1x8v, 2ci0, 2w09, 1h5z, 2vku, 2bz9, 1e9x, 2w0a, 2cib
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  1H5Z	100%	MYCOBACTERIUM TUBERCULOSIS	CYTOCHROME P450 14 ALPHA-STEROL DEMETHYLASE (CYP51) FROM MYCOBACTERIUM TUBERCULOSIS IN FERRIC LOW-SPIN STATE
  1EA1	100%	MYCOBACTERIUM TUBERCULOSIS	Cytochrome P450 14 alpha-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with fluconazole
  1E9X	100%	MYCOBACTERIUM TUBERCULOSIS	Cytochrome P450 14 alpha-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with 4-phenylimidazole
  2W0B	99%	MYCOBACTERIUM TUBERCULOSIS	CYP51 OF M. TUBERCULOSIS BOUND TO AN INHIBITOR 3-{[(4-METHYLPHENYL)SULFONYL]AMINO}PROPYL PYRIDIN-4-YLCARBAMATE
  2W09	99%	MYCOBACTERIUM TUBERCULOSIS	CYP51 OF M. TUBERCULOSIS BOUND TO AN INHIBITOR CIS-4-METHYL-N-[(1S)-3-(METHYLSULFANYL)-1-(PYRIDIN-4-YLCARBAMOYL)PROPYL]CYCLOHEXANECARBOXAMIDE
  2VKU	99%	MYCOBACTERIUM TUBERCULOSIS	4,4'-Dihydroxybenzophenone Mimics Sterol Substrate in the Binding Site of Sterol 14alpha-Demethylase (CYP51) in the X-ray Structure of the Complex
  2CIB	99%	MYCOBACTERIUM TUBERCULOSIS	High throughput screening and x-ray crystallography assisted evaluation of small molecule scaffolds for CYP51 inhibitors
  2CI0	99%	MYCOBACTERIUM TUBERCULOSIS	High throughput screening and x-ray crystallography assisted evaluation of small molecule scaffolds for CYP51 inhibitors
  2BZ9	99%	MYCOBACTERIUM TUBERCULOSIS	Ligand-free structure of sterol 14alpha-demethylase from Mycobacterium tuberculosis in P2(1) space group
  1X8V	99%	Mycobacterium tuberculosis	Estriol-bound and ligand-free structures of sterol 14alpha-demethylase (CYP51)

• Links to additional information on cyp51:
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 1.33 (from Jeremy Rock's lab)
  • BioCyc
  • Systems Biology

Amino Acid Sequence

MSAVALPRVSGGHDEHGHLEEFRTDPIGLMQRVRDECGDVGTFQLAGKQVVLLSGSHANEFFFRAGDDDLDQAKAYPFMTPIFGEGVVFDASPERRKEML
HNAALRGEQMKGHAATIEDQVRRMIADWGEAGEIDLLDFFAELTIYTSSACLIGKKFRDQLDGRFAKLYHELERGTDPLAYVDPYLPIESFRRRDEARNG
LVALVADIMNGRIANPPTDKSDRDMLDVLIAVKAETGTPRFSADEITGMFISMMFAGHHTSSGTASWTLIELMRHRDAYAAVIDELDELYGDGRSVSFHA
LRQIPQLENVLKETLRLHPPLIILMRVAKGEFEVQGHRIHEGDLVAASPAISNRIPEDFPDPHDFVPARYEQPRQEDLLNRWTWIPFGAGRHRCVGAAFA
IMQIKAIFSVLLREYEFEMAQPPESYRNDHSKMVVQLAQPACVRYRRRTGV

Additional Information