Gene Rv0764c
in Mycobacterium tuberculosis H37Rv
General annotation
| Type | CDS |
| Function | Involved in sterol biosynthesis. 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. |
| Product | Cytochrome P450 51 Cyp51 (CYPL1) (P450-L1A1) (sterol 14-alpha demethylase) (lanosterol 14-alpha demethylase) (P450-14DM) |
| Comments | Rv0764c, (MT0788, MTCY369.09c), len: 451 aa. Cyp51, cytochrome P450 51 (sterol 14-alpha demethylase), similar to others e.g. Q16850|CP51_HUMAN cytochrome P450 51 (CYPL1) (P450L1) (sterol 14-alpha demethylase) (lanosterol 14-alpha demethylase) from Homo sapiens (509 aa), FASTA scores: opt: 848, E(): 0, (33.9% identity in 439 aa overlap); NP_172633.1|NC_003070 putative obtusifoliol 14-alpha demethylase from Arabidopsis thaliana (488 aa); P93596|CP51_WHEAT cytochrome P450 51 (CYPL1) (P450-L1A1) (obtusifoliol 14-alpha demethylase) from Triticum aestivum (453 aa); etc. Also similar to many other Mycobacterium tuberculosis cytochromes P450 e.g. Rv1394c, FASTA score: (22.5% identity in 444 aa overlap). Contains PS00086 Cytochrome P450 cysteine heme-iron ligand signature. Belongs to the cytochrome P450 family. |
| Functional category | Intermediary metabolism and respiration |
| Proteomics | Identified by mass spectrometry in whole cell lysates of M. tuberculosis H37Rv but not the culture filtrate or membrane protein fraction (See de Souza et al., 2011). |
| Mutant | Non-essential gene for in vitro growth of H37Rv in a MtbYM rich medium, by Himar1 transposon mutagenesis (see Minato et al. 2019). Non-essential gene for in vitro growth of H37Rv, by analysis of saturated Himar1 transposon libraries (see DeJesus et al. 2017). Non essential gene by Himar1 transposon mutagenesis in H37Rv and CDC1551 strains (see Sassetti et al., 2003 and Lamichhane et al., 2003). Check for mutants available at TARGET website |
Coordinates
| Type | Start | End | Orientation |
|---|---|---|---|
| CDS | 856682 | 858037 | - |
Genomic sequence
Feature type
Upstream flanking region (bp)
Downstream flanking region (bp)
Update
Protein sequence
>Mycobacterium tuberculosis H37Rv|Rv0764c|cyp51
MSAVALPRVSGGHDEHGHLEEFRTDPIGLMQRVRDECGDVGTFQLAGKQVVLLSGSHANEFFFRAGDDDLDQAKAYPFMTPIFGEGVVFDASPERRKEMLHNAALRGEQMKGHAATIEDQVRRMIADWGEAGEIDLLDFFAELTIYTSSACLIGKKFRDQLDGRFAKLYHELERGTDPLAYVDPYLPIESFRRRDEARNGLVALVADIMNGRIANPPTDKSDRDMLDVLIAVKAETGTPRFSADEITGMFISMMFAGHHTSSGTASWTLIELMRHRDAYAAVIDELDELYGDGRSVSFHALRQIPQLENVLKETLRLHPPLIILMRVAKGEFEVQGHRIHEGDLVAASPAISNRIPEDFPDPHDFVPARYEQPRQEDLLNRWTWIPFGAGRHRCVGAAFAIMQIKAIFSVLLREYEFEMAQPPESYRNDHSKMVVQLAQPACVRYRRRTGV
Bibliography
- Aoyama Y et al. [1998]. CYP51-like gene of Mycobacterium tuberculosis actually encodes a P450 similar to eukaryotic CYP51. Product Biochemistry
- Bellamine A, Mangla AT, Nes WD and Waterman MR [1999]. Characterization and catalytic properties of the sterol 14alpha-demethylase from Mycobacterium tuberculosis. Product Biochemistry
- Bellamine A et al. [2001]. Structural requirements for substrate recognition of Mycobacterium tuberculosis 14 alpha-demethylase: implications for sterol biosynthesis. Product Biochemistry
- Podust LM, Stojan J, Poulos TL and Waterman MR [2001]. Substrate recognition sites in 14alpha-sterol demethylase from comparative analysis of amino acid sequences and X-ray structure of Mycobacterium tuberculosis CYP51. Structure
- Podust L. M, Podust LM, Poulos TL and Waterman MR [2001]. Crystal structure of cytochrome P450 14alpha -sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors. Structure
- Lepesheva GI, Virus C and Waterman MR [2003]. Conservation in the CYP51 family. Role of the B' helix/BC loop and helices F and G in enzymatic function. Structure Mutant
- Lamichhane G et al. [2003]. A postgenomic method for predicting essential genes at subsaturation levels of mutagenesis: application to Mycobacterium tuberculosis. Mutant
- Sassetti CM et al. [2003]. Genes required for mycobacterial growth defined by high density mutagenesis. Mutant
- Podust LM et al. [2004]. Estriol bound and ligand-free structures of sterol 14alpha-demethylase. Structure
- Podust LM et al. [2007]. Small-molecule scaffolds for CYP51 inhibitors identified by high-throughput screening and defined by X-ray crystallography. Structure
- Eddine AN, von Kries JP, Podust MV, Warrier T, Kaufmann SH and Podust LM [2008]. X-ray structure of 4,4'-dihydroxybenzophenone mimicking sterol substrate in the active site of sterol 14alpha-demethylase (CYP51). Structure
- de Souza GA et al. [2011]. Bacterial proteins with cleaved or uncleaved signal peptides of the general secretory pathway. Proteomics
- DeJesus MA et al. [2017]. Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis. Mutant
- Minato Y et al. [2019]. Genomewide Assessment of Mycobacterium tuberculosis Conditionally Essential Metabolic Pathways. Mutant
