P0A5Y4 (FABG_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
3-oxoacyl-[acyl-carrier-protein] reductase FabG1
EC=1.1.1.100

Alternative name(s):
3-ketoacyl-acyl carrier protein reductase
Beta-Ketoacyl-acyl carrier protein reductase
Beta-ketoacyl-ACP reductase

Gene names

Name:	fabG1
Synonyms:	mabA
Ordered Locus Names:	Rv1483, MT1530
ORF Names:	MTCY277.04

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	247 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the NADPH-dependent reduction of beta-ketoacyl-ACP substrates to beta-hydroxyacyl-ACP products, the first reductive step in the elongation cycle of fatty acid biosynthesis. MabA preferentially metabolizes long-chain substrates (C8-C20) and has a poor affinity for the C4 substrate. Ref.1 Ref.4 Ref.5
Catalytic activity	(3R)-3-hydroxyacyl-[acyl-carrier-protein] + NADP+ = 3-oxoacyl-[acyl-carrier-protein] + NADPH. Ref.4
Pathway	Lipid metabolism; fatty acid biosynthesis.
Subunit structure	Homotetramer. Ref.4 Ref.6 Ref.7
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family.
Biophysicochemical properties	Kinetic parameters: KM=8.3 µM for beta-Ketododecanoyl-CoA (at 25 degrees Celsius and at pH 7.0) Ref.4 KM=41 µM for NADPH (at 25 degrees Celsius and at pH 7.0) KM=70 µM for beta-Ketooctanoyl-CoA (at 25 degrees Celsius and at pH 7.0) KM=1530 µM for acetoacetyl-CoA (at 25 degrees Celsius and at pH 7.0)
Mass spectrometry	Molecular mass is 27729 Da from positions 2 - 247. Determined by ESI. Recombinant protein expressed in E.coli. Ref.4

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Fatty acid metabolism Lipid biosynthesis Lipid metabolism
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	mycolic acid biosynthetic process Inferred from direct assay Ref.4. Source: MTBBASE protein homotetramerization Inferred from physical interaction Ref.4Ref.6. Source: MTBBASE short-chain fatty acid metabolic process Inferred from direct assay Ref.5. Source: MTBBASE
Cellular_component	plasma membrane Inferred from direct assay PubMed 14532352. Source: MTBBASE
Molecular_function	3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity Inferred from direct assay PubMed 17059223Ref.5Ref.1. Source: MTBBASE NADPH binding Inferred from direct assay Ref.4. Source: UniProtKB acetoacetyl-CoA reductase activity Inferred from direct assay Ref.4. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 247

246

3-oxoacyl-[acyl-carrier-protein] reductase FabG1

PRO_0000054677

Regions

Nucleotide binding

22 – 25

4

NADP

Nucleotide binding

61 – 62

2

NADP

Nucleotide binding

153 – 157

5

NADP By similarity

Sites

Active site

153

1

Proton acceptor By similarity

Binding site

27

1

NADP; via amide nitrogen

Binding site

47

1

NADP

Binding site

88

1

NADP; via amide nitrogen

Binding site

140

1

Substrate By similarity

Binding site

186

1

NADP; via amide nitrogen and carbonyl oxygen By similarity

Experimental info

Mutagenesis

60

1

C → V: Displays a lower activity than the wild-type and a slightly decreased affinity for the cofactor. Totally inactive; when associated with A-139 and L-144. Ref.6 Ref.7

Mutagenesis

139

1

G → A: Complete protein inactivation and freezes the catalytic site into its closed form. Totally inactive; when associated with V-60 and L-144. Ref.7

Mutagenesis

144

1

S → L: Stabilizes the catalytic loop in its open active form. Totally inactive; when associated with V-60 and A-139. Ref.7

Secondary structure

1

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247

Helix Strand Turn

Details...

Beta strand

17 – 20

4

Turn

21 – 24

4

Helix

26 – 37

12

Beta strand

41 – 49

9

Beta strand

55 – 59

5

Helix

65 – 79

15

Beta strand

83 – 88

6

Turn

97 – 99

3

Helix

102 – 112

11

Helix

114 – 129

16

Beta strand

133 – 138

6

Helix

142 – 145

4

Helix

151 – 171

21

Helix

172 – 174

3

Beta strand

176 – 183

8

Helix

189 – 193

5

Helix

196 – 202

7

Helix

203 – 205

3

Helix

214 – 225

12

Helix

227 – 229

3

Beta strand

236 – 240

5

Turn

241 – 244

4

Sequences

	Sequence		Length	Mass (Da)
	P0A5Y4 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: 70F6254B0FFFCD47	FASTA	247	25,697
	10 20 30 40 50 60 MTATATEGAK PPFVSRSVLV TGGNRGIGLA IAQRLAADGH KVAVTHRGSG APKGLFGVEC 70 80 90 100 110 120 DVTDSDAVDR AFTAVEEHQG PVEVLVSNAG LSADAFLMRM TEEKFEKVIN ANLTGAFRVA 130 140 150 160 170 180 QRASRSMQRN KFGRMIFIGS VSGSWGIGNQ ANYAASKAGV IGMARSIARE LSKANVTANV 190 200 210 220 230 240 VAPGYIDTDM TRALDERIQQ GALQFIPAKR VGTPAEVAGV VSFLASEDAS YISGAVIPVD GGMGMGH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The mabA gene from the inhA operon of Mycobacterium tuberculosis encodes a 3-ketoacyl reductase that fails to confer isoniazid resistance." Banerjee A., Sugantino M., Sacchettini J.C., Jacobs W.R. Jr. Microbiology 144:2697-2704(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION AS A BETA-KETOACYL-ACP REDUCTASE. Strain: ATCC 25618 / H37Rv.
[2]	"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.
[3]	"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.
[4]	"MabA (FabG1), a Mycobacterium tuberculosis protein involved in the long-chain fatty acid elongation system FAS-II." Marrakchi H., Ducasse S., Labesse G., Montrozier H., Margeat E., Emorine L., Charpentier X., Daffe M., Quemard A. Microbiology 148:951-960(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN FATTY ACID BIOSYNTHESIS, CATALYTIC ACTIVITY, MASS SPECTROMETRY, SUBSTRATES SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
[5]	"The essential mycobacterial genes, fabG1 and fabG4, encode 3-oxoacyl-thioester reductases that are functional in yeast mitochondrial fatty acid synthase type 2." Gurvitz A. Mol. Genet. Genomics 282:407-416(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A BETA-KETOACYL-ACP REDUCTASE, SUBSTRATES SPECIFICITY.
[6]	"Crystal structure of MabA from Mycobacterium tuberculosis, a reductase involved in long-chain fatty acid biosynthesis." Cohen-Gonsaud M., Ducasse S., Hoh F., Zerbib D., Labesse G., Quemard A. J. Mol. Biol. 320:249-261(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF MUTANT CYS-60 AND WILD-TYPE, MUTAGENESIS OF CYS-60, SUBUNIT, NOMENCLATURE.
[7]	"Lack of dynamics in the MabA active site kills the enzyme activity: practical consequences for drug-design studies." Poncet-Montange G., Ducasse-Cabanot S., Quemard A., Labesse G., Cohen-Gonsaud M. Acta Crystallogr. D 63:923-925(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT VAL-60/ALA-139/LEU-144, MUTAGENESIS OF CYS-60; GLY-139 AND SER-144, SUBUNIT.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U66801 Genomic DNA. Translation: AAC69639.1.
BX842576 Genomic DNA. Translation: CAB02033.1.
AE000516 Genomic DNA. Translation: AAK45795.1.
AL123456 Genomic DNA. Translation: CCP44243.1.

PIR

F70710.

RefSeq

NP_215999.1. NC_000962.3.
NP_335981.1. NC_002755.2.
YP_006514867.1. NC_018143.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UZL	X-ray	2.00	A/B	1-247	[»]
1UZM	X-ray	1.49	A/B	1-247	[»]
1UZN	X-ray	1.91	A/B	1-247	[»]
2NTN	X-ray	2.30	A/B	1-247	[»]

ProteinModelPortal

P0A5Y4.

SMR

P0A5Y4. Positions 9-247.

ModBase

Search...

Protein-protein interaction databases

STRING

83332.Rv1483.

PTM databases

PhosSite

P11091078.

Proteomic databases

PRIDE

P0A5Y4.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAK45795; AAK45795; MT1530.

GeneID

13320076.
886551.
924439.

KEGG

mtc:MT1530.
mtu:Rv1483.
mtv:RVBD_1483.

PATRIC

18125128. VBIMycTub22151_1679.

Organism-specific databases

TubercuList

Rv1483.

Phylogenomic databases

eggNOG

COG1028.

KO

K11610.

OMA

VEAHQGP.

ProtClustDB

CLSK871938.

Enzyme and pathway databases

UniPathway

UPA00094.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

InterPro

IPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
[Graphical view]

Pfam

PF00106. adh_short. 1 hit.
[Graphical view]

PRINTS

PR00081. GDHRDH.
PR00080. SDRFAMILY.

PROSITE

PS00061. ADH_SHORT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P0A5Y4.

Entry information

Entry name

FABG_MYCTU

Accession

Primary (citable) accession number: P0A5Y4
Secondary accession number(s): L0T9R6, P71764, Q48930

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	May 1, 2013
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program