Q79FX6 (MMAA2_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclopropane mycolic acid synthase MmaA2
Short name=CMAS
EC=2.1.1.79

Alternative name(s):
Cyclopropane-fatty-acyl-phospholipid synthase
Short name=CFA synthase
Mycolic acid methyltransferase
Short name=MA-MT
S-adenosylmethionine-dependent methyltransferase
Short name=AdoMet-MT
Short name=SAM-MT

Gene names

Name:	mmaA2
Synonyms:	mma2
Ordered Locus Names:	Rv0644c

Organism

Mycobacterium tuberculosis [Reference proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Actinobacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	287 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the conversion of a double bond to a cis cyclopropane ring at the distal position of an alpha mycolic acid via the transfer of a methylene group from S-adenosyl-L-methionine. MmaA2 also catalyzes the biosynthesis of the cis-cyclopropanated methoxymycolates. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence. Ref.2 Ref.6
Catalytic activity	S-adenosyl-L-methionine + phospholipid olefinic fatty acid = S-adenosyl-L-homocysteine + phospholipid cyclopropane fatty acid.
Enzyme regulation	Inhibited by S-adenosyl-N-decyl-aminoethyl (SADAE) and thiacetazone (TAC). Ref.3 Ref.5
Pathway	Lipid metabolism; mycolic acid biosynthesis.
Disruption phenotype	Disruption of this gene suppresses a cyclopropane group at the distal position of alpha mycolic acid and cause a mild impairment in methoxymycolate, but not in ketomycolate. A 2-fold reduction in the relative abundance of cis-cyclopropanated methoxymycolate is observed. Cells lacking both cmA2 and mmaA2 genes cannot cis cyclopropanate methoxymycolates or ketomycolates. Ref.2
Sequence similarities	Belongs to the CFA/CMAS family.

Ontologies

Keywords
Biological process	Lipid biosynthesis Lipid metabolism
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	mycolic acid biosynthetic process Inferred from direct assay Ref.6PubMed 9694888. Source: MTBBASE
Cellular_component	cell wall Inferred from direct assay PubMed 20825248. Source: MTBBASE plasma membrane Inferred from direct assay PubMed 14532352. Source: MTBBASE
Molecular_function	cyclopropane-fatty-acyl-phospholipid synthase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 287

287

Cyclopropane mycolic acid synthase MmaA2

PRO_0000398359

Regions

Region

33 – 34

2

S-adenosyl-L-methionine binding

Region

72 – 74

3

S-adenosyl-L-methionine binding

Region

94 – 99

6

S-adenosyl-L-methionine binding

Region

123 – 124

2

S-adenosyl-L-methionine binding

Sites

Active site

269

1

By similarity

Binding site

136

1

S-adenosyl-L-methionine; via carbonyl oxygen

Secondary structure

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287

Helix Strand Turn

Details...

Helix

9 – 16

8

Helix

20 – 24

5

Helix

45 – 57

13

Turn

58 – 61

4

Beta strand

67 – 72

6

Helix

77 – 86

10

Beta strand

89 – 95

7

Helix

97 – 108

12

Beta strand

116 – 121

6

Helix

123 – 125

3

Beta strand

131 – 137

7

Helix

139 – 142

4

Helix

144 – 146

3

Helix

147 – 157

11

Beta strand

163 – 171

9

Helix

174 – 179

6

Helix

186 – 198

13

Helix

208 – 218

11

Beta strand

221 – 227

7

Helix

229 – 245

17

Helix

247 – 253

7

Helix

256 – 275

20

Beta strand

277 – 286

10

Sequences

	Sequence		Length	Mass (Da)
	Q79FX6 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 669C3224C6B178C0	FASTA	287	32,724
	10 20 30 40 50 60 MVNDLTPHFE DVQAHYDLSD DFFRLFLDPT QTYSCAHFER EDMTLEEAQI AKIDLALGKL 70 80 90 100 110 120 GLQPGMTLLD IGCGWGATMR RAIAQYDVNV VGLTLSKNQA AHVQKSFDEM DTPRDRRVLL 130 140 150 160 170 180 AGWEQFNEPV DRIVSIGAFE HFGHDRHADF FARAHKILPP DGVLLLHTIT GLTRQQMVDH 190 200 210 220 230 240 GLPLTLWLAR FLKFIATEIF PGGQPPTIEM VEEQSAKTGF TLTRRQSLQP HYARTLDLWA 250 260 270 280 EALQEHKSEA IAIQSEEVYE RYMKYLTGCA KLFRVGYIDV NQFTLAK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"The mmaA2 gene of Mycobacterium tuberculosis encodes the distal cyclopropane synthase of the alpha-mycolic acid." Glickman M.S. J. Biol. Chem. 278:7844-7849(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN THE BIOSYNTHESIS OF CYCLOPROPANE RING IN THE ALPHA MYCOLATE, DISRUPTION PHENOTYPE. Strain: ATCC 35801 / TMC 107 / Erdman.
[3]	"Thiacetazone, an antitubercular drug that inhibits cyclopropanation of cell wall mycolic acids in mycobacteria." Alahari A., Trivelli X., Guerardel Y., Dover L.G., Besra G.S., Sacchettini J.C., Reynolds R.C., Coxon G.D., Kremer L. PLoS ONE 2:E1343-E1343(2007) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION. Strain: ATCC 25618 / H37Rv.
[4]	"targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis." Raman K., Yeturu K., Chandra N. BMC Syst. Biol. 2:109-109(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
[5]	"S-adenosyl-N-decyl-aminoethyl, a potent bisubstrate inhibitor of mycobacterium tuberculosis mycolic acid methyltransferases." Vaubourgeix J., Bardou F., Boissier F., Julien S., Constant P., Ploux O., Daffe M., Quemard A., Mourey L. J. Biol. Chem. 284:19321-19330(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION. Strain: ATCC 25618 / H37Rv.
[6]	"Redundant function of cmaA2 and mmaA2 in Mycobacterium tuberculosis cis cyclopropanation of oxygenated mycolates." Barkan D., Rao V., Sukenick G.D., Glickman M.S. J. Bacteriol. 192:3661-3668(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN OXYGEN-CONTAINING MYCOLATES AND IN ALPHA-MYCOLATES BIOSYNTHESIS.
[7]	"Structure of the cyclopropane synthase mmaA2 from Mycobacterium tuberculosis." Smith C.V., Sacchettini J.C. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH S-ADENOSYLMETHIONINE. Strain: ATCC 25618 / H37Rv.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BX842574 Genomic DNA. Translation: CAB07103.1.
AL123456 Genomic DNA. Translation: CCP43387.1.

RefSeq

NP_215158.1. NC_000962.3.
YP_006513985.1. NC_018143.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TPY	X-ray	2.20	A	1-287	[»]

ProteinModelPortal

Q79FX6.

SMR

Q79FX6. Positions 3-287.

ModBase

Search...

Protein-protein interaction databases

STRING

83332.Rv0644c.

Proteomic databases

PRIDE

Q79FX6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

13318530.
888061.

KEGG

mtu:Rv0644c.
mtv:RVBD_0644c.

PATRIC

18149942. VBIMycTub87468_0719.

Organism-specific databases

TubercuList

Rv0644c.

Phylogenomic databases

eggNOG

COG2230.

HOGENOM

HOG000245191.

KO

K00574.

OMA

PAKFSLI.

ProtClustDB

CLSK790562.

Enzyme and pathway databases

BioCyc

MetaCyc:RV0644C-MONOMER.

UniPathway

UPA00915.

Family and domain databases

InterPro

IPR003333. Mycolic_cyclopropane_synthase.
[Graphical view]

Pfam

PF02353. CMAS. 1 hit.
[Graphical view]

PIRSF

PIRSF003085. CMAS. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

Q79FX6.

Entry information

Entry name

MMAA2_MYCTU

Accession

Primary (citable) accession number: Q79FX6
Secondary accession number(s): L0T7B6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 5, 2010
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program