Cyclopropane mycolic acid synthase 3

Details

Name
Cyclopropane mycolic acid synthase 3
Synonyms
  • 2.1.1.79
  • AdoMet-MT
  • CFA synthase
  • cma3
  • cmaA3
  • CMAS
  • CMAS-3
  • Cyclopropane fatty acid synthase
  • Cyclopropane-fatty-acyl-phospholipid synthase
  • MA-MT
  • Mycolic acid methyltransferase
  • S-adenosylmethionine-dependent methyltransferase
  • SAM-MT
Gene Name
pcaA
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Amino acid sequence
>lcl|BSEQ0051138|Cyclopropane mycolic acid synthase 3
MSVQLTPHFGNVQAHYDLSDDFFRLFLDPTQTYSCAYFERDDMTLQEAQIAKIDLALGKL
NLEPGMTLLDIGCGWGATMRRAIEKYDVNVVGLTLSENQAGHVQKMFDQMDTPRSRRVLL
EGWEKFDEPVDRIVSIGAFEHFGHQRYHHFFEVTHRTLPADGKMLLHTIVRPTFKEGREK
GLTLTHELVHFTKFILAEIFPGGWLPSIPTVHEYAEKVGFRVTAVQSLQLHYARTLDMWA
TALEANKDQAIAIQSQTVYDRYMKYLTGCAKLFRQGYTDVDQFTLEK
Number of residues
287
Molecular Weight
33027.5
Theoretical pI
Not Available
GO Classification
Functions
cyclopropane-fatty-acyl-phospholipid synthase activity
Processes
active evasion of host immune response / modulation by symbiont of host innate immune response / mycolic acid biosynthetic process / pathogenesis / S-adenosylmethionine metabolic process
Components
cytoplasm
General Function
Involved in the phagosome maturation block (PMB). Catalyzes the conversion of a double bond to a cyclopropane ring at the proximal position of an alpha mycolic acid via the transfer of a methylene group from S-adenosyl-L-methionine. It can use cis, cis 11,14-eicosadienoic acid and linoelaidic acid as substrate. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence.
Specific Function
Cyclopropane-fatty-acyl-phospholipid synthase activity
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051139|Cyclopropane mycolic acid synthase 3 (pcaA)
ATGTCCGTGCAGCTCACGCCGCATTTTGGAAACGTGCAAGCTCATTACGACCTCTCCGAC
GACTTTTTCCGGCTGTTCTTGGACCCCACCCAGACCTACAGCTGTGCCTACTTCGAACGC
GACGACATGACGCTGCAGGAGGCCCAGATCGCCAAGATCGACCTGGCCCTGGGCAAGCTG
AACCTCGAACCCGGGATGACGTTGCTGGACATCGGCTGCGGCTGGGGCGCGACCATGCGG
CGCGCCATCGAGAAATACGACGTCAATGTCGTGGGCCTGACGTTGTCGGAGAACCAGGCC
GGTCATGTCCAGAAAATGTTCGACCAAATGGACACCCCCCGCTCCAGACGAGTGTTGCTG
GAGGGATGGGAGAAATTTGACGAGCCCGTCGACCGCATCGTCTCGATCGGCGCGTTCGAG
CACTTCGGCCACCAGCGCTACCACCATTTCTTCGAGGTGACCCACCGCACGTTGCCGGCC
GACGGCAAGATGTTGCTGCACACCATCGTGCGCCCCACCTTCAAAGAAGGCAGGGAAAAG
GGCCTGACGTTGACCCACGAACTGGTTCACTTCACCAAATTCATCCTGGCCGAGATCTTC
CCCGGTGGCTGGCTGCCGTCCATCCCGACGGTGCACGAGTACGCCGAGAAGGTCGGCTTC
CGGGTCACCGCGGTCCAGTCATTGCAGCTGCACTACGCCAGGACGCTGGACATGTGGGCC
ACAGCGCTCGAGGCCAACAAAGATCAGGCCATCGCGATCCAGTCGCAGACTGTCTACGAC
CGCTACATGAAGTACCTGACCGGCTGCGCGAAGCTGTTCCGCCAGGGTTACACCGACGTC
GACCAGTTCACACTGGAAAAGTAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP9WPB3
UniProtKB Entry NameCMAS3_MYCTU
General References
  1. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG: Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537-44. [PubMed:9634230]
  2. Glickman MS, Cox JS, Jacobs WR Jr: A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. Mol Cell. 2000 Apr;5(4):717-27. [PubMed:10882107]
  3. Alahari A, Trivelli X, Guerardel Y, Dover LG, Besra GS, Sacchettini JC, Reynolds RC, Coxon GD, Kremer L: Thiacetazone, an antitubercular drug that inhibits cyclopropanation of cell wall mycolic acids in mycobacteria. PLoS One. 2007 Dec 19;2(12):e1343. [PubMed:18094751]
  4. Raman K, Yeturu K, Chandra N: targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis. BMC Syst Biol. 2008 Dec 19;2:109. doi: 10.1186/1752-0509-2-109. [PubMed:19099550]
  5. Barkan D, Liu Z, Sacchettini JC, Glickman MS: Mycolic acid cyclopropanation is essential for viability, drug resistance, and cell wall integrity of Mycobacterium tuberculosis. Chem Biol. 2009 May 29;16(5):499-509. doi: 10.1016/j.chembiol.2009.04.001. [PubMed:19477414]
  6. Vaubourgeix J, Bardou F, Boissier F, Julien S, Constant P, Ploux O, Daffe M, Quemard A, Mourey L: S-adenosyl-N-decyl-aminoethyl, a potent bisubstrate inhibitor of mycobacterium tuberculosis mycolic acid methyltransferases. J Biol Chem. 2009 Jul 17;284(29):19321-30. doi: 10.1074/jbc.M809599200. Epub 2009 May 13. [PubMed:19439410]
  7. Kelkar DS, Kumar D, Kumar P, Balakrishnan L, Muthusamy B, Yadav AK, Shrivastava P, Marimuthu A, Anand S, Sundaram H, Kingsbury R, Harsha HC, Nair B, Prasad TS, Chauhan DS, Katoch K, Katoch VM, Kumar P, Chaerkady R, Ramachandran S, Dash D, Pandey A: 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. [PubMed:21969609]
  8. Corrales RM, Molle V, Leiba J, Mourey L, de Chastellier C, Kremer L: Phosphorylation of mycobacterial PcaA inhibits mycolic acid cyclopropanation: consequences for intracellular survival and for phagosome maturation block. J Biol Chem. 2012 Jul 27;287(31):26187-99. doi: 10.1074/jbc.M112.373209. Epub 2012 May 23. [PubMed:22621931]
  9. Huang CC, Smith CV, Glickman MS, Jacobs WR Jr, Sacchettini JC: Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis. J Biol Chem. 2002 Mar 29;277(13):11559-69. Epub 2001 Dec 26. [PubMed:11756461]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01752S-adenosyl-L-homocysteineexperimentalunknownDetails