Q7D9R5 (CMAS3_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclopropane mycolic acid synthase 3
Short name=CMAS
EC=2.1.1.79

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

Gene names

Name:	pcaA
Synonyms:	cma3, cmaA3, CMAS-3
Ordered Locus Names:	Rv0470c, MT0486

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	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. Ref.3 Ref.8
Catalytic activity	S-adenosyl-L-methionine + phospholipid olefinic fatty acid = S-adenosyl-L-homocysteine + phospholipid cyclopropane fatty acid. Ref.8
Enzyme regulation	Regulated by PknF. Inhibited by S-adenosyl-N-decyl-aminoethyl (SADAE), thiacetazone (TAC) and dioctylamine. Ref.4 Ref.6 Ref.7
Pathway	Lipid metabolism; mycolic acid biosynthesis.
Subunit structure	Homodimer. Ref.9
Subcellular location	Cytoplasm By similarity.
Post-translational modification	Phosphorylation by PknF at Thr-168 and Thr-183 regulates the mycolic acid profile which affects colonial cording, intramacrophage replication and abrogates the PMB.
Disruption phenotype	Inactivation of pcaA does not affect initial growth of the organism over the first 3 weeks, but after 6 weeks, when wild-type organisms persist at a constant level indefinitely, the pcaA mutant is progressively eliminated from the animal. Cells lacking this gene accumulates a hybrid mycolate with a cis double bond at the proximal position in place of the cis cyclopropane present in wild-type alpha mycolate. Ref.3 Ref.8
Miscellaneous	Was identified as a high-confidence drug target.
Sequence similarities	Belongs to the CFA/CMAS family.

Ontologies

Keywords
Biological process	Lipid biosynthesis Lipid metabolism
Cellular component	Cytoplasm
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	S-adenosylmethionine metabolic process Inferred from direct assay Ref.9. Source: MTBBASE active evasion of host immune response Inferred from mutant phenotype PubMed 17353284. Source: MTBBASE modulation by symbiont of host innate immune response Inferred from mutant phenotype PubMed 15710652. Source: MTBBASE mycolic acid biosynthetic process Inferred from direct assay Ref.3. Source: MTBBASE pathogenesis Inferred from direct assay Ref.3. Source: MTBBASE
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cyclopropane-fatty-acyl-phospholipid synthase activity Inferred from mutant phenotype Ref.3. Source: MTBBASE
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 3

PRO_0000398358

Regions

Region

33 – 34

2

S-adenosyl-L-methionine binding

Region

68 – 76

9

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

Amino acid modifications

Modified residue

168

1

Phosphothreonine Ref.8

Modified residue

183

1

Phosphothreonine Ref.8

Experimental info

Mutagenesis

168

1

T → A: Loss of phosphorylation; when associated with A-183. Ref.8

Mutagenesis

183

1

T → A: Loss of phosphorylation; when associated with A-168. Ref.8

Secondary structure

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287

Helix Strand Turn

Details...

Helix

20 – 23

4

Turn

24 – 26

3

Helix

45 – 58

14

Turn

59 – 61

3

Beta strand

67 – 72

6

Helix

77 – 86

10

Beta strand

89 – 95

7

Helix

97 – 109

13

Beta strand

116 – 121

6

Helix

123 – 125

3

Beta strand

131 – 137

7

Helix

139 – 141

3

Helix

144 – 146

3

Helix

147 – 157

11

Beta strand

163 – 171

9

Beta strand

177 – 180

4

Helix

189 – 198

10

Helix

208 – 216

9

Turn

217 – 219

3

Beta strand

221 – 227

7

Helix

229 – 245

17

Helix

247 – 253

7

Helix

256 – 274

19

Beta strand

279 – 286

8

Sequences

	Sequence		Length	Mass (Da)
	Q7D9R5 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: B8D2999A4CD81112	FASTA	287	33,028
	10 20 30 40 50 60 MSVQLTPHFG NVQAHYDLSD DFFRLFLDPT QTYSCAYFER DDMTLQEAQI AKIDLALGKL 70 80 90 100 110 120 NLEPGMTLLD IGCGWGATMR RAIEKYDVNV VGLTLSENQA GHVQKMFDQM DTPRSRRVLL 130 140 150 160 170 180 EGWEKFDEPV DRIVSIGAFE HFGHQRYHHF FEVTHRTLPA DGKMLLHTIV RPTFKEGREK 190 200 210 220 230 240 GLTLTHELVH FTKFILAEIF PGGWLPSIPT VHEYAEKVGF RVTAVQSLQL HYARTLDMWA 250 260 270 280 TALEANKDQA IAIQSQTVYD RYMKYLTGCA KLFRQGYTDV DQFTLEK

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]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis." Glickman M.S., Cox J.S., Jacobs W.R. Jr. Mol. Cell 5:717-727(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN THE BIOSYNTHESIS OF CYCLOPROPANE RING IN THE ALPHA MYCOLATE, DISRUPTION PHENOTYPE, NOMENCLATURE. Strain: ATCC 25618 / H37Rv.
[4]	"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.
[5]	"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].
[6]	"Mycolic acid cyclopropanation is essential for viability, drug resistance, and cell wall integrity of Mycobacterium tuberculosis." Barkan D., Liu Z., Sacchettini J.C., Glickman M.S. Chem. Biol. 16:499-509(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[7]	"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.
[8]	"Phosphorylation of mycobacterial PcaA inhibits mycolic acid cyclopropanation: consequences for intracellular survival and for phagosome maturation block." Corrales R.M., Molle V., Leiba J., Mourey L., de Chastellier C., Kremer L. J. Biol. Chem. 287:26187-26199(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT THR-168 AND THR-183, MUTAGENESIS OF THR-168 AND THR-183, DISRUPTION PHENOTYPE, SUBSTRATE SPECIFICITY.
[9]	"Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis." Huang C.-C., Smith C.V., Glickman M.S., Jacobs W.R. Jr., Sacchettini J.C. J. Biol. Chem. 277:11559-11569(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE, SUBUNIT. Strain: ATCC 25618 / H37Rv.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BX842573 Genomic DNA. Translation: CAE55286.1.
AE000516 Genomic DNA. Translation: AAK44709.1.
AL123456 Genomic DNA. Translation: CCP43203.1.

PIR

B70829.

RefSeq

NP_334895.1. NC_002755.2.
YP_006513799.1. NC_018143.1.
YP_177730.1. NC_000962.3.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1L1E	X-ray	2.00	A/B	1-287	[»]

ProteinModelPortal

Q7D9R5.

SMR

Q7D9R5. Positions 16-287.

ModBase

Search...

Protein-protein interaction databases

STRING

83332.Rv0470c.

Proteomic databases

PRIDE

Q7D9R5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAK44709; AAK44709; MT0486.

GeneID

13318340.
886284.
923834.

KEGG

mtc:MT0486.
mtu:Rv0470c.
mtv:RVBD_0470c.

PATRIC

18122780. VBIMycTub22151_0524.

Organism-specific databases

TubercuList

Rv0470c.

Phylogenomic databases

eggNOG

COG2230.

HOGENOM

HOG000245191.

KO

K00574.

OMA

MASAWLR.

ProtClustDB

CLSK790562.

Enzyme and pathway databases

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

Q7D9R5.

Entry information

Entry name

CMAS3_MYCTU

Accession

Primary (citable) accession number: Q7D9R5
Secondary accession number(s): L0T6K4, Q6MX38

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 5, 2010
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program