Gene - combatTB X

cyp125

Type: protein_coding
Name: cyp125
Locus Name: Rv3545c
Product: Probable cytochrome P450 125 Cyp125
Functional Category: Intermediary metabolism and respiration
Location: 3984144..3985445 (- strand)
Gene Length: 1301 bp
Nucleotides: GTGTCGTGGAATCACCAGTCAGTGGAGATTGCAGTAAGGAGAACTACCGTGCCCAGCCCCAATCTGCCGCCCGGGTTCGATTTCACCGACCCCGCAATCTACGCCGAACGGCTGCCGGTTGCCGAATTCGCCGAGCTGCGGTCCGCGGCGCCGATCTGGTGGAACGGGCAGGATCCTGGCAAGGGCGGCGGCTTTCACGACGGCGGTTTCTGGGCGATCACCAAACTCAACGACGTCAAAGAGATATCGCGGCATAGCGACGTGTTCTCCAGCTACGAAAACGGGGTGATCCCGCGATTCAAGAACGACATCGCGCGTGAGGACATCGAGGTTCAGCGCTTCGTCATGCTCAACATGGACGCGCCGCACCACACCCGGCTGCGCAAGATCATCTCTCGCGGCTTCACGCCACGTGCGGTCGGACGCCTGCATGACGAGCTCCAGGAGCGCGCCCAGAAGATCGCCGCGGAGGCGGCCGCCGCGGGTTCTGGAGACTTTGTCGAGCAGGTTTCCTGTGAGCTGCCATTGCAGGCGATCGCGGGCTTGCTGGGCGTGCCGCAGGAGGACCGCGGCAAGCTGTTCCACTGGTCAAACGAGATGACCGGCAACGAGGATCCGGAATACGCCCACATCGATCCGAAGGCGTCCTCGGCGGAGCTGATCGGCTATGCGATGAAGATGGCCGAGGAGAAGGCGAAGAACCCCGCCGACGACATCGTGACTCAGTTGATCCAAGCCGATATCGACGGCGAGAAGCTCTCCGACGACGAGTTCGGCTTCTTCGTGGTGATGCTGGCGGTGGCCGGTAACGAGACCACCCGCAACTCCATCACCCAGGGCATGATGGCGTTCGCTGAACACCCCGACCAGTGGGAGCTGTACAAGAAAGTGCGTCCGGAGACCGCGGCCGATGAGATCGTGCGCTGGGCAACCCCGGTCACCGCTTTTCAGCGCACCGCGCTGCGGGACTACGAGTTGTCCGGCGTACAGATTAAGAAGGGTCAGCGGGTGGTGATGTTCTACCGGTCGGCTAACTTCGACGAAGAGGTTTTCCAGGATCCGTTCACATTTAACATCCTGCGCAACCCCAACCCGCACGTCGGCTTCGGCGGCACCGGCGCTCACTACTGCATCGGTGCGAATCTGGCCCGGATGACGATCAACCTAATCTTTAACGCCGTAGCCGACCACATGCCCGACCTCAAGCCGATCTCGGCGCCCGAGCGGCTGCGGTCCGGCTGGCTCAACGGCATTAAGCACTGGCAGGTCGACTACACCGGTAGATGCCCGGTTGCTCACTA
Drug Resistance: Check for drug resistance association at TBDREAMDB
Mutations: Check for mutants available at TARGET

Function

Involved in the utilization of cholesterol as the sole carbon and energy source by degrading the side chain during infection (PubMed:20843794, PubMed:20545858). Primarily catalyzes the sequential oxidation of the terminal methyl of cholest-4-en-3-one into (25S)-26-hydroxycholest-4-en-3-one (alcohol), (25S)-26-oxocholest-4-en-3-one (aldehyde), to finally yield the carboxylic acid (25S)-3-oxocholest-4-en-26-oate (PubMed:19846551, PubMed:20843794, PubMed:20545858). Also able to sequentially oxidize cholesterol itself, not only cholest-4-en-3-one (PubMed:19846551, PubMed:20843794, PubMed:20545858). {ECO:0000269|PubMed:19846551, ECO:0000269|PubMed:20545858, ECO:0000269|PubMed:20843794}.

Family

Cytochrome P450 family

GO

cholesterol catabolic process GO:0006707 biological_process
cholest-4-en-3-one 26-monooxygenase activity GO:0036199 molecular_function
steroid hydroxylase activity GO:0008395 molecular_function
iron ion binding GO:0005506 molecular_function
pathogenesis GO:0009405 biological_process
heme binding GO:0020037 molecular_function
growth of symbiont in host GO:0044117 biological_process

InterPro

UniProt: P9WPP1
GenBank: Rv3545c
EnsemblBacteria: Rv3545c
Mycobrowser: Rv3545c

PDB IDs:

Summary

Name: Steroid C26-monooxygenase (EC 1.14.15.29) (Cholest-4-en-3-one 26-monooxygenase) (Cholest-4-en-3-one C26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming]) (Cholesterol C26-monooxygenase) (Cholesterol C26-monooxygenase [(25S)-3beta-hydroxycholest-5-en-26-oate forming]) (Cytochrome P450 125) (Steroid C27-monooxygenase)
Family: Cytochrome P450 family
Protein Sequence: MSWNHQSVEIAVRRTTVPSPNLPPGFDFTDPAIYAERLPVAEFAELRSAAPIWWNGQDPGKGGGFHDGGFWAITKLNDVKEISRHSDVFSSYENGVIPRFKNDIAREDIEVQRFVMLNMDAPHHTRLRKIISRGFTPRAVGRLHDELQERAQKIAAEAAAAGSGDFVEQVSCELPLQAIAGLLGVPQEDRGKLFHWSNEMTGNEDPEYAHIDPKASSAELIGYAMKMAEEKAKNPADDIVTQLIQADIDGEKLSDDEFGFFVVMLAVAGNETTRNSITQGMMAFAEHPDQWELYKKVRPETAADEIVRWATPVTAFQRTALRDYELSGVQIKKGQRVVMFYRSANFDEEVFQDPFTFNILRNPNPHVGFGGTGAHYCIGANLARMTINLIFNAVADHMPDLKPISAPERLRSGWLNGIKHWQVDYTGRCPVAH
Mass: 48,433 Da
Length: 433 Aa

Rv3545c doesn't seem to be a targeted by any drug.

Steroid degradation mtu00984
mtu00984
PATHWAY_MAP mtu00984 Steroid degradation

Reverse type I inhibitor of Mycobacterium tuberculosis CYP125A1.: Bioorg Med Chem Lett. 2011 Jan 1;21(1):332-7. doi: 10.1016/j.bmcl.2010.11.007. Epub 2010 Nov 5.
Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest-4-en-3-one.: Mol Microbiol. 2010 Aug;77(3):730-42. doi: 10.1111/j.1365-2958.2010.07243.x. Epub 2010 Jun 10.
The Structure of Mycobacterium tuberculosis CYP125: molecular basis for cholesterol binding in a P450 needed for host infection.: J Biol Chem. 2009 Dec 18;284(51):35524-33. doi: 10.1074/jbc.M109.032706.
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.
Functional redundancy of steroid C26-monooxygenase activity in Mycobacterium tuberculosis revealed by biochemical and genetic analyses.: J Biol Chem. 2010 Nov 19;285(47):36352-60. doi: 10.1074/jbc.M110.161117. Epub 2010 Sep 15.
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.
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.: Nature. 1998 Jun 11;393(6685):537-44. doi: 10.1038/31159.