Cyclopropane mycolic acid synthase 2

Details

Name
Cyclopropane mycolic acid synthase 2
Synonyms
  • 2.1.1.79
  • AdoMet-MT
  • CFA synthase
  • cma2
  • CMAS
  • CMAS-2
  • Cyclopropane fatty acid synthase
  • Cyclopropane-fatty-acyl-phospholipid synthase
  • MA-MT
  • Mycolic acid methyltransferase
  • S-adenosylmethionine-dependent methyltransferase
  • SAM-MT
Gene Name
cmaA2
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Amino acid sequence
>lcl|BSEQ0051161|Cyclopropane mycolic acid synthase 2
MTSQGDTTSGTQLKPPVEAVRSHYDKSNEFFKLWLDPSMTYSCAYFERPDMTLEEAQYAK
RKLALDKLNLEPGMTLLDIGCGWGSTMRHAVAEYDVNVIGLTLSENQYAHDKAMFDEVDS
PRRKEVRIQGWEEFDEPVDRIVSLGAFEHFADGAGDAGFERYDTFFKKFYNLTPDDGRML
LHTITIPDKEEAQELGLTSPMSLLRFIKFILTEIFPGGRLPRISQVDYYSSNAGWKVERY
HRIGANYVPTLNAWADALQAHKDEAIALKGQETYDIYMHYLRGCSDLFRDKYTDVCQFTL
VK
Number of residues
302
Molecular Weight
34659.795
Theoretical pI
Not Available
GO Classification
Functions
cyclopropane-fatty-acyl-phospholipid synthase activity
Processes
Actinobacterium-type cell wall biogenesis / modulation by symbiont of host innate immune response / mycolate cell wall layer assembly / mycolic acid biosynthetic process / response to hypoxia / S-adenosylmethionine metabolic process
Components
cytosol / plasma membrane
General Function
Catalyzes the formation of trans cyclopropanated ketomycolate or methoxymycolate through the conversion of a double bond to a cyclopropane ring at the proximal position of an oxygenated mycolic acid via the transfer of a methylene group from S-adenosyl-L-methionine. In the absence of MmaA2, CmaA2 has a non-specific cis-cyclopropanating activity and is able to catalyze the conversion of a double bond to a cis cyclopropane ring at the distal position of an alpha mycolic acid. 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|BSEQ0051162|Cyclopropane mycolic acid synthase 2 (cmaA2)
ATGACGTCACAGGGCGACACGACAAGCGGCACGCAGCTCAAGCCGCCGGTCGAAGCAGTT
CGATCCCACTACGACAAATCGAACGAGTTCTTCAAGCTCTGGCTTGACCCATCGATGACG
TACAGCTGCGCCTACTTCGAACGTCCCGATATGACGCTGGAAGAGGCGCAGTACGCGAAG
CGCAAGCTGGCACTGGACAAGCTGAACCTTGAGCCCGGCATGACGCTGCTCGACATCGGC
TGCGGCTGGGGTTCCACCATGCGACACGCGGTCGCCGAGTACGACGTCAACGTCATCGGC
TTGACCCTGAGCGAAAACCAGTACGCCCACGACAAGGCGATGTTCGATGAGGTCGACAGC
CCCCGCCGAAAAGAGGTGCGAATCCAGGGCTGGGAGGAGTTCGACGAGCCGGTCGACCGC
ATCGTGTCACTCGGTGCGTTTGAGCATTTCGCCGACGGTGCCGGGGACGCCGGGTTCGAG
CGCTACGACACCTTCTTCAAGAAGTTCTACAATTTGACGCCCGACGACGGCCGGATGCTG
CTGCACACCATCACTATCCCGGACAAAGAGGAAGCCCAGGAGCTGGGCTTGACGTCTCCG
ATGAGCCTGCTGCGCTTCATCAAGTTCATCCTGACCGAGATCTTCCCGGGCGGGCGGCTG
CCCAGGATCTCGCAGGTGGACTATTACTCCTCCAACGCCGGATGGAAGGTCGAGCGCTAC
CACCGGATCGGGGCCAACTACGTGCCGACCCTGAACGCCTGGGCGGATGCGCTACAGGCG
CACAAAGATGAGGCGATCGCCCTCAAGGGCCAGGAGACGTACGACATCTACATGCACTAC
CTACGTGGCTGCTCAGACCTGTTCCGCGACAAGTACACGGACGTCTGCCAGTTCACTCTG
GTCAAATAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP9WPB5
UniProtKB Entry NameCMAS2_MYCTU
General References
  1. George KM, Yuan Y, Sherman DR, Barry CE 3rd: The biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Identification and functional analysis of CMAS-2. J Biol Chem. 1995 Nov 10;270(45):27292-8. [PubMed:7592990]
  2. 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]
  3. Glickman MS, Cahill SM, Jacobs WR Jr: The Mycobacterium tuberculosis cmaA2 gene encodes a mycolic acid trans-cyclopropane synthetase. J Biol Chem. 2001 Jan 19;276(3):2228-33. Epub 2000 Nov 22. [PubMed:11092877]
  4. Rao V, Gao F, Chen B, Jacobs WR Jr, Glickman MS: Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis -induced inflammation and virulence. J Clin Invest. 2006 Jun;116(6):1660-7. [PubMed:16741578]
  5. 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]
  6. 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]
  7. 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]
  8. Barkan D, Rao V, Sukenick GD, Glickman MS: Redundant function of cmaA2 and mmaA2 in Mycobacterium tuberculosis cis cyclopropanation of oxygenated mycolates. J Bacteriol. 2010 Jul;192(14):3661-8. doi: 10.1128/JB.00312-10. Epub 2010 May 14. [PubMed:20472794]
  9. 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]
  10. 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
DB04221Didecyldimethylammoniumapproved, experimentalunknownDetails