Gene - combatTB X

fadA5

Type: protein_coding
Name: fadA5
Locus Name: Rv3546
Product: Probable acetyl-CoA acetyltransferase FadA5 (acetoacetyl-CoA thiolase)
Functional Category: Lipid metabolism
Location: 3985557..3986732 (+ strand)
Gene Length: 1175 bp
Nucleotides: TGGGTTACCCGGTCATCGTTGAAGCCACCCGCAGCCCCATCGGCAAACGCAACGGATGGCTGTCGGGGCTGCATGCCACCGAGTTGTTGGGCGCGGTGCAAAAGGCGGTGGTCGACAAGGCCGGCATCCAGTCCGGCCTTCACGCCGGTGACGTCGAACAGGTCATCGGCGGTTGCGTGACCCAGTTCGGGGAGCAATCCAACAACATCAGCCGGGTGGCCTGGCTGACGGCCGGTTTGCCCGAACACGTCGGCGCCACCACCGTCGACTGCCAGTGCGGCAGCGGCCAGCAGGCCAACCATCTGATTGCCGGGTTGATCGCGGCCGGTGCCATCGATGTCGGCATCGCCTGCGGCATCGAGGCGATGAGCCGGGTCGGGCTGGGCGCCAACGCCGGGCCGGACCGCTCGCTGATCCGCGCGCAGTCATGGGATATCGACCTGCCGAACCAGTTCGAGGCCGCCGAGCGGATCGCCAAGCGGCGCGGCATCACCCGCGAGGACGTGGATGTCTTCGGGCTCGAGTCGCAGCGACGCGCGCAGCGGGCCTGGGCGGAGGGCCGCTTTGACCGCGAGATCTCGCCGATCCAGGCGCCGGTGCTCGACGAGCAGAATCAGCCCACCGGCGAGCGGCGCCTGGTCTTTCGCGACCAGGGCCTGCGCGAGACCACGATGGCGGGGCTAGGCGAGCTGAAACCGGTGCTCGAGGGCGGCATCCACACCGCGGGCACGTCGTCGCAGATCTCCGACGGCGCGGCAGCCGTGTTGTGGATGGACGAAGCCGTGGCACGTGCGCACGGCCTGACCCCGCGGGCCCGGATCGTCGCCCAGGCACTCGTCGGCGCCGAGCCCTACTACCACCTGGACGGCCCGGTGCAGTCCACCGCGAAGGTGCTGGAGAAGGCCGGCATGAAGATCGGCGACATCGACATCGTCGAGATCAACGAGGCGTTCGCGTCCGTGGTGCTGTCCTGGGCGCGGGTGCACGAGCCCGACATGGACCGGGTCAACGTCAACGGCGGGGCGATCGCGCTGGGGCATCCGGTGGGCTGCACCGGCAGCCGGCTGATCACCACCGCCCTGCACGAGCTCGAGCGCACCGACCAGAGCCTCGCGCTGATCACCATGTGCGCCGGCGGGGCCCTGTCCACCGGCACCATCATCGAGCGGATTTAA
Drug Resistance: Check for drug resistance association at TBDREAMDB
Mutations: Check for mutants available at TARGET

Function

Involved in the beta-oxidation of the cholesterol side chain (PubMed:19822655). It is important for utilization of cholesterol as a sole carbon source in vitro and for full virulence in the chronic stage of mouse lung infection (PubMed:19822655). Catalyzes the thiolysis of 3,22-dioxochol-4-en-24-oyl-CoA to yield 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA) and acetyl-CoA (PubMed:25482540). Also able to use acetoacetyl-CoA (AcAcCoA) as substrate (PubMed:19822655). {ECO:0000269|PubMed:19822655, ECO:0000269|PubMed:25482540}.

Family

Thiolase-like superfamily, Thiolase family

GO

fatty acid beta-oxidation GO:0006635 biological_process
cholesterol catabolic process GO:0006707 biological_process
identical protein binding GO:0042802 molecular_function
acetyl-CoA C-acyltransferase activity GO:0003988 molecular_function
pathogenesis GO:0009405 biological_process
phenylacetate catabolic process GO:0010124 biological_process

InterPro

UniProt: I6XHI4
GenBank: Rv3546
EnsemblBacteria: Rv3546
Mycobrowser: Rv3546

Summary

Name: Steroid 3-ketoacyl-CoA thiolase (EC 2.3.1.16) (Acetyl-CoA acetyltransferase FadA5) (Beta-ketoacyl-CoA thiolase)
Family: Thiolase-like superfamily, Thiolase family
Protein Sequence: MGYPVIVEATRSPIGKRNGWLSGLHATELLGAVQKAVVDKAGIQSGLHAGDVEQVIGGCVTQFGEQSNNISRVAWLTAGLPEHVGATTVDCQCGSGQQANHLIAGLIAAGAIDVGIACGIEAMSRVGLGANAGPDRSLIRAQSWDIDLPNQFEAAERIAKRRGITREDVDVFGLESQRRAQRAWAEGRFDREISPIQAPVLDEQNQPTGERRLVFRDQGLRETTMAGLGELKPVLEGGIHTAGTSSQISDGAAAVLWMDEAVARAHGLTPRARIVAQALVGAEPYYHLDGPVQSTAKVLEKAGMKIGDIDIVEINEAFASVVLSWARVHEPDMDRVNVNGGAIALGHPVGCTGSRLITTALHELERTDQSLALITMCAGGALSTGTIIERI
Mass: 41,329 Da
Length: 391 Aa

Rv3546 doesn't seem to be a targeted by any drug.

Two-component system mtu02020
mtu02020
Environmental Information Processing; Signal transduction

Terpenoid backbone biosynthesis mtu00900
mtu00900
Metabolism; Metabolism of terpenoids and polyketides

Butanoate metabolism mtu00650
mtu00650
PATHWAY_MAP mtu00650 Butanoate metabolism

Propanoate metabolism mtu00640
mtu00640
PATHWAY_MAP mtu00640 Propanoate metabolism

Glyoxylate and dicarboxylate metabolism mtu00630
mtu00630
PATHWAY_MAP mtu00630 Glyoxylate and dicarboxylate metabolism

Pyruvate metabolism mtu00620
mtu00620
PATHWAY_MAP mtu00620 Pyruvate metabolism

Tryptophan metabolism mtu00380
mtu00380
PATHWAY_MAP mtu00380 Tryptophan metabolism

Benzoate degradation mtu00362
mtu00362
PATHWAY_MAP mtu00362 Benzoate degradation

Fatty acid degradation mtu00071
mtu00071
PATHWAY_MAP mtu00071 Fatty acid degradation

Synthesis and degradation of ketone bodies mtu00072
mtu00072
PATHWAY_MAP mtu00072 Synthesis and degradation of ketone bodies

Valine, leucine and isoleucine degradation mtu00280
mtu00280
PATHWAY_MAP mtu00280 Valine, leucine and isoleucine degradation

Lysine degradation mtu00310
mtu00310
PATHWAY_MAP mtu00310 Lysine degradation

FadA5 a thiolase from Mycobacterium tuberculosis: a steroid-binding pocket reveals the potential for drug development against tuberculosis.: Structure. 2015 Jan 6;23(1):21-33. doi: 10.1016/j.str.2014.10.010. Epub 2014 Dec 4.
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.
A thiolase of Mycobacterium tuberculosis is required for virulence and production of androstenedione and androstadienedione from cholesterol.: Infect Immun. 2010 Jan;78(1):275-82. doi: 10.1128/IAI.00893-09. Epub 2009 Oct 12.
Re-annotation of the genome sequence of Mycobacterium tuberculosis H37Rv.: Microbiology. 2002 Oct;148(Pt 10):2967-73. doi: 10.1099/00221287-148-10-2967.
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.: Nature. 1998 Jun 11;393(6685):537-44. doi: 10.1038/31159.