Hydroxymycolate synthase MmaA4

Details

Name
Hydroxymycolate synthase MmaA4
Synonyms
  • 2.1.1.-
  • AdoMet-MT
  • hma
  • MA-MT
  • mma4
  • Mycolic acid methyltransferase
  • S-adenosylmethionine-dependent methyltransferase
  • SAM-MT
Gene Name
mmaA4
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Amino acid sequence
>lcl|BSEQ0012694|Hydroxymycolate synthase MmaA4
MTRMAEKPISPTKTRTRFEDIQAHYDVSDDFFALFQDPTRTYSCAYFEPPELTLEEAQYA
KVDLNLDKLDLKPGMTLLDIGCGWGTTMRRAVERFDVNVIGLTLSKNQHARCEQVLASID
TNRSRQVLLQGWEDFAEPVDRIVSIEAFEHFGHENYDDFFKRCFNIMPADGRMTVQSSVS
YHPYEMAARGKKLSFETARFIKFIVTEIFPGGRLPSTEMMVEHGEKAGFTVPEPLSLRPH
YIKTLRIWGDTLQSNKDKAIEVTSEEVYNRYMKYLRGCEHYFTDEMLDCSLVTYLKPGAA
A
Number of residues
301
Molecular Weight
34670.13
Theoretical pI
5.44
GO Classification
Functions
methyltransferase activity / S-adenosylmethionine-dependent methyltransferase activity
Processes
mycolic acid biosynthetic process
Components
cell wall / plasma membrane
General Function
S-adenosylmethionine-dependent methyltransferase activity
Specific Function
Involved in the biosynthesis of hydroxymycolate, a common precursor of oxygenated mycolic acids (methoxy-mycolate and keto-mycolate). Probably transfers a methyl group from the S-adenosylmethionine (SAM) cofactor and, subsequently or simultaneously, a water molecule onto the double bound of ethylene substrates, leading to the formation of the hydroxylated product at the distal position. Involved in the activation of the antitubercular drug thiacetazone (TAC).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0012695|Hydroxymycolate synthase MmaA4 (mmaA4)
ATGACGAGAATGGCCGAGAAACCGATTAGCCCAACCAAGACACGGACACGCTTCGAAGAC
ATCCAAGCGCACTACGACGTCTCCGATGATTTCTTCGCCCTGTTCCAGGACCCGACCCGA
ACTTACAGCTGTGCCTACTTCGAGCCACCGGAGCTCACGCTCGAAGAAGCCCAATACGCC
AAGGTCGACCTCAACCTGGACAAGCTGGACCTCAAGCCGGGCATGACGCTGCTGGACATT
GGGTGCGGTTGGGGCACCACCATGAGGCGCGCCGTCGAGCGGTTCGACGTTAACGTCATC
GGCCTGACGTTGTCCAAGAACCAGCACGCCCGCTGCGAGCAAGTGCTGGCTTCGATCGAC
ACCAACCGCTCACGTCAAGTGCTGCTGCAAGGCTGGGAGGATTTCGCCGAACCCGTCGAC
CGGATTGTGTCGATCGAAGCCTTCGAGCACTTCGGGCACGAGAACTACGACGACTTCTTC
AAGCGGTGTTTCAACATCATGCCCGCCGACGGCCGGATGACCGTCCAGAGCAGCGTCAGC
TACCACCCCTACGAGATGGCGGCCCGCGGTAAGAAGCTGAGCTTCGAGACGGCGCGTTTC
ATCAAGTTCATCGTCACCGAGATATTTCCCGGCGGCCGCCTGCCGTCCACCGAGATGATG
GTCGAACACGGCGAGAAGGCCGGTTTCACCGTCCCGGAGCCGCTCTCGTTGCGCCCGCAT
TACATCAAGACGCTGCGGATCTGGGGGGACACGCTGCAGTCCAATAAGGACAAGGCCATC
GAGGTCACCTCCGAAGAGGTCTACAACCGCTACATGAAGTATTTGCGTGGCTGCGAGCAC
TACTTCACCGACGAGATGCTCGACTGCAGCCTGGTGACCTACCTCAAGCCGGGTGCCGCG
GCCTAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ79FX8
UniProtKB Entry NameMMAA4_MYCTU
GenBank Protein ID2222772
GenBank Gene IDBX842574
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. [Article]
  2. Dubnau E, Chan J, Raynaud C, Mohan VP, Laneelle MA, Yu K, Quemard A, Smith I, Daffe M: Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice. Mol Microbiol. 2000 May;36(3):630-7. [Article]
  3. Dinadayala P, Laval F, Raynaud C, Lemassu A, Laneelle MA, Laneelle G, Daffe M: Tracking the putative biosynthetic precursors of oxygenated mycolates of Mycobacterium tuberculosis. Structural analysis of fatty acids of a mutant strain deviod of methoxy- and ketomycolates. J Biol Chem. 2003 Feb 28;278(9):7310-9. Epub 2002 Dec 6. [Article]
  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. [Article]
  5. Dao DN, Sweeney K, Hsu T, Gurcha SS, Nascimento IP, Roshevsky D, Besra GS, Chan J, Porcelli SA, Jacobs WR: Mycolic acid modification by the mmaA4 gene of M. tuberculosis modulates IL-12 production. PLoS Pathog. 2008 Jun 6;4(6):e1000081. doi: 10.1371/journal.ppat.1000081. [Article]
  6. Alahari A, Alibaud L, Trivelli X, Gupta R, Lamichhane G, Reynolds RC, Bishai WR, Guerardel Y, Kremer L: Mycolic acid methyltransferase, MmaA4, is necessary for thiacetazone susceptibility in Mycobacterium tuberculosis. Mol Microbiol. 2009 Mar;71(5):1263-77. doi: 10.1111/j.1365-2958.2009.06604.x. Epub 2009 Jan 15. [Article]
  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. [Article]
  8. Boissier F, Bardou F, Guillet V, Uttenweiler-Joseph S, Daffe M, Quemard A, Mourey L: Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. J Biol Chem. 2006 Feb 17;281(7):4434-45. Epub 2005 Dec 15. [Article]
  9. 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. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB074135'-S-[2-(decylamino)ethyl]-5'-thioadenosineexperimentalunknownDetails