Reviewed, UniProtKB/Swiss-Prot P0A6R0 (FABH_ECOLI)

Names and origin

Protein names

Recommended name:
    3-oxoacyl-[acyl-carrier-protein] synthase 3
    EC=2.3.1.180
Alternative name(s):
    3-oxoacyl-[acyl-carrier-protein] synthase III
    Beta-ketoacyl-ACP synthase III
      Short name=KAS III
    EcFabH

Gene names

Name:	fabH
Ordered Locus Names:	b1091, JW1077

Organism

Escherichia coli (strain K12) [Complete proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia

Protein attributes

Sequence length	317 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Has some substrate specificity for acetyl-CoA. Its substrate specificity determines the biosynthesis of straight-chain of fatty acids instead of branched-chain. HAMAP MF_01815
Catalytic activity	Acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacetyl-[acyl-carrier-protein] + CoA + CO2. HAMAP MF_01815
Enzyme regulation	Negatively regulated by acyl-ACP, possibly by binding to either the free enzyme or the acyl-enzyme intermediate. Ref.8
Pathway	Lipid metabolism; fatty acid biosynthesis. HAMAP MF_01815
Subunit structure	Homodimer. HAMAP MF_01815
Subcellular location	Cytoplasm HAMAP MF_01815.
Domain	The last Arg residue of the ACP-binding site is essential for the weak association between ACP/acpP and fabH. Ref.9
Miscellaneous	Inhibited by the SB418011 antibiotic. Not inhibited by cerulenin and thiolactomycin. HAMAP MF_01815
Sequence similarities	Belongs to the fabH family.

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Lipid synthesis
Cellular component	Cytoplasm
Molecular function	Acyltransferase Transferase
Technical term	3D-structure Complete proteome Direct protein sequencing Multifunctional enzyme
Gene Ontology (GO)
Biological process	fatty acid biosynthetic process Inferred from electronic annotation. Source: HAMAP
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	3-oxoacyl-[acyl-carrier-protein] synthase activity Inferred from electronic annotation. Source: HAMAP beta-ketoacyl-acyl-carrier-protein synthase III 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 – 317

317

3-oxoacyl-[acyl-carrier-protein] synthase 3 HAMAP MF_01815

PRO_0000110424

Regions

Region

245 – 249

5

ACP-binding HAMAP MF_01815

Sites

Active site

112

1

HAMAP MF_01815

Active site

244

1

HAMAP MF_01815

Active site

274

1

HAMAP MF_01815

Experimental info

Mutagenesis

112

1

C → S: Loss of activity.

Mutagenesis

214

1

K → E or A: Strongly reduces the binding to malonyl-ACP but not that of the substrate. Ref.9

Mutagenesis

244

1

H → A: Loss of activity.

Mutagenesis

249

1

R → E or A: Abolishes the binding to malonyl-ACP but not that of the substrate. Ref.9

Mutagenesis

253

1

A → Y: Abolishes both binding to malonyl-ACP and binding to substrate. Ref.9

Mutagenesis

256 – 257

2

KK → AA: Strongly reduces both binding to malonyl-ACP and binding to substrate.

Mutagenesis

256 – 257

2

KK → EE: Abolishes the binding to malonyl-ACP but not that of the substrate.

Mutagenesis

274

1

N → A: Loss of activity.

Secondary structure

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317

Helix Strand Turn

Details...

Beta strand

2 – 11

10

Beta strand

14 – 18

5

Helix

19 – 23

5

Helix

30 – 37

8

Beta strand

41 – 44

4

Helix

51 – 66

16

Helix

70 – 72

3

Beta strand

75 – 79

5

Beta strand

84 – 88

5

Helix

90 – 98

9

Beta strand

105 – 109

5

Helix

111 – 113

3

Helix

114 – 127

14

Beta strand

132 – 140

9

Helix

142 – 145

4

Helix

151 – 154

4

Beta strand

160 – 171

12

Beta strand

173 – 181

9

Helix

183 – 188

6

Beta strand

189 – 192

4

Helix

209 – 230

22

Helix

235 – 237

3

Beta strand

240 – 243

4

Helix

248 – 257

10

Helix

262 – 264

3

Helix

269 – 272

4

Helix

276 – 278

3

Helix

279 – 289

11

Beta strand

298 – 305

8

Turn

306 – 308

3

Beta strand

309 – 316

8

Sequences

	Sequence		Length	Mass (Da)
	P0A6R0-1 [UniParc]. Last modified May 10, 2005. Version 1. Checksum: BF3192CFF36023D3	FASTA	317	33,515
	10 20 30 40 50 60 MYTKIIGTGS YLPEQVRTNA DLEKMVDTSD EWIVTRTGIR ERHIAAPNET VSTMGFEAAT 70 80 90 100 110 120 RAIEMAGIEK DQIGLIVVAT TSATHAFPSA ACQIQSMLGI KGCPAFDVAA ACAGFTYALS 130 140 150 160 170 180 VADQYVKSGA VKYALVVGSD VLARTCDPTD RGTIIIFGDG AGAAVLAASE EPGIISTHLH 190 200 210 220 230 240 ADGSYGELLT LPNADRVNPE NSIHLTMAGN EVFKVAVTEL AHIVDETLAA NNLDRSQLDW 250 260 270 280 290 300 LVPHQANLRI ISATAKKLGM SMDNVVVTLD RHGNTSAASV PCALDEAVRD GRIKPGQLVL 310 LEAFGGGFTW GSALVRF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of the beta-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12." Tsay J.-T., Oh W., Larson T.J., Jackowski S., Rock C.O. J. Biol. Chem. 267:6807-6814(1992) [PubMed: 1551888] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-30. Strain: K12.
[2]	"The complete genome sequence of Escherichia coli K-12." Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y. Science 277:1453-1474(1997) [PubMed: 9278503] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[3]	"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T. Mol. Syst. Biol. 2:E1-E5(2006) [PubMed: 16738553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[4]	"Physical locations of genes in the rne (ams)-rpmF-plsX-fab region of the Escherichia coli K-12 chromosome." Oh W., Larson T.J. J. Bacteriol. 174:7873-7874(1992) [PubMed: 1447160] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-76. Strain: K12.
[5]	"Cloning, nucleotide sequence, and expression of the Escherichia coli fabD gene, encoding malonyl coenzyme A-acyl carrier protein transacylase." Verwoert I.I.G.S., Verbree E.C., van der Linden K.H., Nijkamp H.J., Stuitje A.R. J. Bacteriol. 174:2851-2857(1992) [PubMed: 1314802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 147-317.
[6]	"Cloning and nucleotide sequence of the fabD gene encoding malonyl coenzyme A-acyl carrier protein transacylase of Escherichia coli." Magnuson K., Oh W., Larson T.J., Cronan J.E. Jr. FEBS Lett. 299:262-266(1992) [PubMed: 1339356] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 201-317. Strain: K12.
[7]	"A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map." Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K., Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S., Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K. , Mori H., Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G., Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M., Horiuchi T. DNA Res. 3:137-155(1996) [PubMed: 8905232] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 201-317. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[8]	"Inhibition of beta-ketoacyl-acyl carrier protein synthase III (FabH) by acyl-acyl carrier protein in Escherichia coli." Heath R.J., Rock C.O. J. Biol. Chem. 271:10996-11000(1996) [PubMed: 8631920] [Abstract] Cited for: ENZYME REGULATION.
[9]	"Identification and analysis of the acyl carrier protein (ACP) docking site on beta-ketoacyl-ACP synthase III." Zhang Y.-M., Rao M.S., Heath R.J., Price A.C., Olson A.J., Rock C.O., White S.W. J. Biol. Chem. 276:8231-8238(2001) [PubMed: 11078736] [Abstract] Cited for: DOMAIN, MUTAGENESIS OF LYS-214; ARG-249; ALA-253 AND 256-LYS-LYS-257.
[10]	"Identification, substrate specificity, and inhibition of the Streptococcus pneumoniae beta-ketoacyl-acyl carrier protein synthase III (FabH)." Khandekar S.S., Gentry D.R., Van Aller G.S., Warren P., Xiang H., Silverman C., Doyle M.L., Chambers P.A., Konstantinidis A.K., Brandt M., Daines R.A., Lonsdale J.T. J. Biol. Chem. 276:30024-30030(2001) [PubMed: 11375394] [Abstract] Cited for: INHIBITION BY ANTIBIOTICS.
[11]	"Crystal structure of beta-ketoacyl-acyl carrier protein synthase III. A key condensing enzyme in bacterial fatty acid biosynthesis." Qiu X., Janson C.A., Konstantinidis A.K., Nwagwu S., Silverman C., Smith W.W., Khandekar S., Lonsdale J., Abdel-Meguid S.S. J. Biol. Chem. 274:36465-36471(1999) [PubMed: 10593943] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[12]	"The 1.8-A crystal structure and active-site architecture of beta-ketoacyl-acyl carrier protein synthase III (FabH) from Escherichia coli." Davies C., Heath R.J., White S.W., Rock C.O. Structure 8:185-195(2000) [PubMed: 10673437] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[13]	"Refined structures of beta-ketoacyl-acyl carrier protein synthase III." Qiu X., Janson C.A., Smith W.W., Head M., Lonsdale J., Konstantinidis A.K. J. Mol. Biol. 307:341-356(2001) [PubMed: 11243824] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M77744 Genomic DNA. Translation: AAA23749.1.
M96793 Genomic DNA. Translation: AAB59065.1.
U00096 Genomic DNA. Translation: AAC74175.1.
AP009048 Genomic DNA. Translation: BAA35899.2.
M87040 Genomic DNA. Translation: AAA23741.1.
Z11565 Genomic DNA. Translation: CAA77659.1.

PIR

A42431.

RefSeq

AP_001717.1.
NP_415609.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EBL	X-ray	1.80	A/B	1-317	[»]
1HN9	X-ray	2.00	A/B	1-317	[»]
1HND	X-ray	1.60	A	1-317	[»]
1HNH	X-ray	1.90	A	1-317	[»]
1HNJ	X-ray	1.46	A	1-317	[»]
1HNK	X-ray	1.90	A	1-317	[»]
1MZS	X-ray	2.10	A	1-317	[»]
2EFT	X-ray	2.00	A/B	1-317	[»]
2GYO	X-ray	2.00	A/B	1-317	[»]
3IL9	X-ray	1.85	A/B	1-317	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P0A6R0.

2-D gel databases

2DBase-Ecoli

P0A6R0.

Genome annotation databases

GeneID

946003.

GenomeReviews

Gene locus JW1077 in contig AP009048_GR.
Gene locus b1091 in contig U00096_GR.

KEGG

ecj:JW1077.
eco:b1091.

Organism-specific databases

EchoBASE

EB0273.

EcoGene

EG10277. fabH.

CMR

Search...

Phylogenomic databases

eggNOG

COG0332.

HOGENOM

HBG649927.

OMA

GGCAGFC.

Enzyme and pathway databases

BioCyc

EcoCyc:FABH-MONOMER.
ECOL168927:B1091-MONOMER.
MetaCyc:FABH-MONOMER.

BRENDA

2.3.1.180. 189382.

Gene expression databases

Genevestigator

P0A6R0.

Family and domain databases

HAMAP

MF_01815. FabH.
[Tree]

InterPro

IPR013751. ACP_syn_III.
IPR013747. ACP_syn_III_C.
IPR004655. FabH_synth.
IPR016039. Thiolase-like.
IPR016038. Thiolase-like_subgr.
[Graphical view]

Gene3D

G3DSA:3.40.47.10. Thiolase-like_subgr. 2 hits.

Pfam

PF08545. ACP_syn_III. 1 hit.
PF08541. ACP_syn_III_C. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00747. fabH. 1 hit.

ProtoNet

Search...

Other Resources

DrugBank

DB01034. Cerulenin.

Entry information

Entry name

FABH_ECOLI

Accession

Primary (citable) accession number: P0A6R0
Secondary accession number(s): P24249

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2005
Last sequence update:	May 10, 2005
Last modified:	February 9, 2010
This is version 56 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)