3HHD

Structure of the Human Fatty Acid Synthase KS-MAT Didomain as a Framework for Inhibitor Design.

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2 Family	KASAT domain-like	8045093	4004293	SCOP2 (2022-06-29)
A	SCOP2 Family	Thiolase-related	8055821	4000245	SCOP2 (2022-06-29)
A	SCOP2 Family	FabD-like	8055823	4003614	SCOP2 (2022-06-29)
A	SCOP2 Family	Probable ACP-binding domain of malonyl-CoA ACP transacylase	8055825	4001289	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	KASAT domain-like	8055820	3002319	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Thiolase-like	8055822	3000122	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	FabD/lysophospholipase-like	8055824	3001121	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Probable ACP-binding domain of malonyl-CoA ACP transacylase	8055826	3001224	SCOP2 (2022-06-29)
C	SCOP2B Superfamily	Thiolase-like	8055822	3000122	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	FabD/lysophospholipase-like	8055824	3001121	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	FabD/lysophospholipase-like	8055824	3001121	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	KASAT domain-like	8055820	3002319	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	KASAT domain-like	8055820	3002319	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Probable ACP-binding domain of malonyl-CoA ACP transacylase	8055826	3001224	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Thiolase-like	8055822	3000122	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	KASAT domain-like	8055820	3002319	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Probable ACP-binding domain of malonyl-CoA ACP transacylase	8055826	3001224	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	FabD/lysophospholipase-like	8055824	3001121	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	KASAT domain-like	8055820	3002319	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	FabD/lysophospholipase-like	8055824	3001121	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	FabD/lysophospholipase-like	8055824	3001121	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	KASAT domain-like	8055820	3002319	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Thiolase-like	8055822	3000122	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	KASAT domain-like	8055820	3002319	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	FabD/lysophospholipase-like	8055824	3001121	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Probable ACP-binding domain of malonyl-CoA ACP transacylase	8055826	3001224	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Acyl_transf_1_2nd	e3hhdA2	A: a+b two layers	X: Alpha-beta plaits	H: Probable ACP-binding domain of malonyl-CoA ACP transacylase (From Topology)	T: Probable ACP-binding domain of malonyl-CoA ACP transacylase	F: Acyl_transf_1_2nd	ECOD (1.6)
A	KAsynt_C_assoc	e3hhdA5	A: a+b two layers	X: KS-MAT linker domain in fatty acid synthase (From Topology)	H: KS-MAT linker domain in fatty acid synthase (From Topology)	T: KS-MAT linker domain in fatty acid synthase	F: KAsynt_C_assoc	ECOD (1.6)
A	Acyl_transf_1_1st	e3hhdA1	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Class I glutamine amidotransferase-like	T: FabD/lysophospholipase-like	F: Acyl_transf_1_1st	ECOD (1.6)
A	ketoacyl-synt	e3hhdA4	A: a/b three-layered sandwiches	X: Thiolase-like (From Topology)	H: Thiolase-like (From Topology)	T: Thiolase-like	F: ketoacyl-synt	ECOD (1.6)
A	Ketoacyl-synt_C	e3hhdA3	A: a/b three-layered sandwiches	X: Thiolase-like (From Topology)	H: Thiolase-like (From Topology)	T: Thiolase-like	F: Ketoacyl-synt_C	ECOD (1.6)
C	Acyl_transf_1_2nd	e3hhdC8	A: a+b two layers	X: Alpha-beta plaits	H: Probable ACP-binding domain of malonyl-CoA ACP transacylase (From Topology)	T: Probable ACP-binding domain of malonyl-CoA ACP transacylase	F: Acyl_transf_1_2nd	ECOD (1.6)
C	KAsynt_C_assoc	e3hhdC5	A: a+b two layers	X: KS-MAT linker domain in fatty acid synthase (From Topology)	H: KS-MAT linker domain in fatty acid synthase (From Topology)	T: KS-MAT linker domain in fatty acid synthase	F: KAsynt_C_assoc	ECOD (1.6)
C	Acyl_transf_1_1st	e3hhdC6	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Class I glutamine amidotransferase-like	T: FabD/lysophospholipase-like	F: Acyl_transf_1_1st	ECOD (1.6)
C	ketoacyl-synt	e3hhdC7	A: a/b three-layered sandwiches	X: Thiolase-like (From Topology)	H: Thiolase-like (From Topology)	T: Thiolase-like	F: ketoacyl-synt	ECOD (1.6)
C	Ketoacyl-synt_C	e3hhdC9	A: a/b three-layered sandwiches	X: Thiolase-like (From Topology)	H: Thiolase-like (From Topology)	T: Thiolase-like	F: Ketoacyl-synt_C	ECOD (1.6)
D	Acyl_transf_1_2nd	e3hhdD8	A: a+b two layers	X: Alpha-beta plaits	H: Probable ACP-binding domain of malonyl-CoA ACP transacylase (From Topology)	T: Probable ACP-binding domain of malonyl-CoA ACP transacylase	F: Acyl_transf_1_2nd	ECOD (1.6)
D	KAsynt_C_assoc	e3hhdD5	A: a+b two layers	X: KS-MAT linker domain in fatty acid synthase (From Topology)	H: KS-MAT linker domain in fatty acid synthase (From Topology)	T: KS-MAT linker domain in fatty acid synthase	F: KAsynt_C_assoc	ECOD (1.6)
D	Acyl_transf_1_1st	e3hhdD6	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Class I glutamine amidotransferase-like	T: FabD/lysophospholipase-like	F: Acyl_transf_1_1st	ECOD (1.6)
D	ketoacyl-synt	e3hhdD7	A: a/b three-layered sandwiches	X: Thiolase-like (From Topology)	H: Thiolase-like (From Topology)	T: Thiolase-like	F: ketoacyl-synt	ECOD (1.6)
D	Ketoacyl-synt_C	e3hhdD9	A: a/b three-layered sandwiches	X: Thiolase-like (From Topology)	H: Thiolase-like (From Topology)	T: Thiolase-like	F: Ketoacyl-synt_C	ECOD (1.6)
B	Acyl_transf_1_2nd	e3hhdB8	A: a+b two layers	X: Alpha-beta plaits	H: Probable ACP-binding domain of malonyl-CoA ACP transacylase (From Topology)	T: Probable ACP-binding domain of malonyl-CoA ACP transacylase	F: Acyl_transf_1_2nd	ECOD (1.6)
B	KAsynt_C_assoc	e3hhdB5	A: a+b two layers	X: KS-MAT linker domain in fatty acid synthase (From Topology)	H: KS-MAT linker domain in fatty acid synthase (From Topology)	T: KS-MAT linker domain in fatty acid synthase	F: KAsynt_C_assoc	ECOD (1.6)
B	Acyl_transf_1_1st	e3hhdB6	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Class I glutamine amidotransferase-like	T: FabD/lysophospholipase-like	F: Acyl_transf_1_1st	ECOD (1.6)
B	ketoacyl-synt	e3hhdB7	A: a/b three-layered sandwiches	X: Thiolase-like (From Topology)	H: Thiolase-like (From Topology)	T: Thiolase-like	F: ketoacyl-synt	ECOD (1.6)
B	Ketoacyl-synt_C	e3hhdB9	A: a/b three-layered sandwiches	X: Thiolase-like (From Topology)	H: Thiolase-like (From Topology)	T: Thiolase-like	F: Ketoacyl-synt_C	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.47.10	Alpha Beta	3-Layer(aba) Sandwich	Peroxisomal Thiolase	Chain A, domain 1	CATH (4.3.0)
A	3.30.70.3290	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits		CATH (4.3.0)
A	3.40.366.10	Alpha Beta	3-Layer(aba) Sandwich	Malonyl-Coenzyme A Acyl Carrier Protein	domain 2	CATH (4.3.0)
A	3.30.70.250	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	Malonyl-CoA ACP transacylase, ACP-binding	CATH (4.3.0)
A	1.10.287.1960	Mainly Alpha	Orthogonal Bundle	Helix Hairpins		CATH (4.3.0)
C	3.40.47.10	Alpha Beta	3-Layer(aba) Sandwich	Peroxisomal Thiolase	Chain A, domain 1	CATH (4.3.0)
C	3.30.70.3290	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits		CATH (4.3.0)
C	3.40.366.10	Alpha Beta	3-Layer(aba) Sandwich	Malonyl-Coenzyme A Acyl Carrier Protein	domain 2	CATH (4.3.0)
C	3.30.70.250	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	Malonyl-CoA ACP transacylase, ACP-binding	CATH (4.3.0)
C	1.10.287.1960	Mainly Alpha	Orthogonal Bundle	Helix Hairpins		CATH (4.3.0)
D	3.40.47.10	Alpha Beta	3-Layer(aba) Sandwich	Peroxisomal Thiolase	Chain A, domain 1	CATH (4.3.0)
D	3.30.70.3290	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits		CATH (4.3.0)
D	3.40.366.10	Alpha Beta	3-Layer(aba) Sandwich	Malonyl-Coenzyme A Acyl Carrier Protein	domain 2	CATH (4.3.0)
D	3.30.70.250	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	Malonyl-CoA ACP transacylase, ACP-binding	CATH (4.3.0)
D	1.10.287.1960	Mainly Alpha	Orthogonal Bundle	Helix Hairpins		CATH (4.3.0)
B	3.40.47.10	Alpha Beta	3-Layer(aba) Sandwich	Peroxisomal Thiolase	Chain A, domain 1	CATH (4.3.0)
B	3.30.70.3290	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits		CATH (4.3.0)
B	3.40.366.10	Alpha Beta	3-Layer(aba) Sandwich	Malonyl-Coenzyme A Acyl Carrier Protein	domain 2	CATH (4.3.0)
B	3.30.70.250	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	Malonyl-CoA ACP transacylase, ACP-binding	CATH (4.3.0)
B	1.10.287.1960	Mainly Alpha	Orthogonal Bundle	Helix Hairpins		CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF02801	Beta-ketoacyl synthase, C-terminal domain (Ketoacyl-synt_C)	Beta-ketoacyl synthase, C-terminal domain	The structure of beta-ketoacyl synthase is similar to that of the thiolase family (Pfam:PF00108) and also chalcone synthase. The active site of beta-ketoacyl synthase is located between the N and C-terminal domains.	Domain
A, B, C, D	PF00109	Beta-ketoacyl synthase, N-terminal domain (ketoacyl-synt)	Beta-ketoacyl synthase, N-terminal domain	The structure of beta-ketoacyl synthase is similar to that of the thiolase family (Pfam:PF00108) and also chalcone synthase. The active site of beta-ketoacyl synthase is located between the N and C-terminal domains. The N-terminal domain contains m ...	The structure of beta-ketoacyl synthase is similar to that of the thiolase family (Pfam:PF00108) and also chalcone synthase. The active site of beta-ketoacyl synthase is located between the N and C-terminal domains. The N-terminal domain contains most of the structures involved in dimer formation and also the active site cysteine [1].	Domain
A, B, C, D	PF16197	Ketoacyl-synthetase C-terminal extension (KAsynt_C_assoc)	Ketoacyl-synthetase C-terminal extension	-	Family
A, B, C, D	PF00698	Acyl transferase domain (Acyl_transf_1)	Acyl transferase domain		Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	Fatty acid synthase	3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity oxidoreductase activity oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor oxidoreductase activity, acting on CH-OH group of donors catalytic activity acetyltransferase activity acyltransferase activity [acyl-carrier-protein] S-acetyltransferase activity acyltransferase activity, transferring groups other than amino-acyl groups transferase activity S-acetyltransferase activity S-acyltransferase activity 3-oxoacyl-[acyl-carrier-protein] synthase activity malonyltransferase activity 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity oxidoreductase activity oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor oxidoreductase activity, acting on CH-OH group of donors catalytic activity acetyltransferase activity acyltransferase activity [acyl-carrier-protein] S-acetyltransferase activity acyltransferase activity, transferring groups other than amino-acyl groups transferase activity S-acetyltransferase activity S-acyltransferase activity 3-oxoacyl-[acyl-carrier-protein] synthase activity malonyltransferase activity [acyl-carrier-protein] S-malonyltransferase activity S-malonyltransferase activity cell adhesion molecule binding cadherin binding protein binding binding fatty acid synthase activity vitamin binding amide binding modified amino acid binding phosphopantetheine binding small molecule binding fatty acyl-[ACP] hydrolase activity hydrolase activity, acting on ester bonds thiolester hydrolase activity hydrolase activity RNA binding nucleic acid binding enoyl-[acyl-carrier-protein] reductase activity (NAD(P)H) oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor oxidoreductase activity, acting on the CH-CH group of donors enoyl-[acyl-carrier-protein] reductase (NADPH) activity (3R)-hydroxyacyl-[acyl-carrier-protein] dehydratase activity hydro-lyase activity lyase activity carbon-oxygen lyase activity	response to interleukin-4 response to peptide response to stimulus response to chemical response to cytokine cellular response to cytokine stimulus cellular response to interleukin-4 developmental process epithelium development endothelial cell differentiation cellular developmental process endothelium development cell development tissue development response to interleukin-4 response to peptide response to stimulus response to chemical response to cytokine cellular response to cytokine stimulus cellular response to interleukin-4 developmental process epithelium development endothelial cell differentiation cellular developmental process endothelium development cell development tissue development epithelial cell differentiation endothelial cell development establishment of endothelial intestinal barrier epithelial cell development cell differentiation establishment of endothelial barrier anatomical structure development cellular process mammary gland development gland development animal organ development glycerol ether metabolic process ether metabolic process glycerol ether biosynthetic process lipid biosynthetic process primary metabolic process ether biosynthetic process biosynthetic process ether lipid metabolic process metabolic process small molecule metabolic process ether lipid biosynthetic process lipid metabolic process myeloid leukocyte differentiation hemopoiesis mononuclear cell differentiation myeloid cell differentiation monocyte differentiation leukocyte differentiation glandular epithelial cell development glandular epithelial cell differentiation columnar/cuboidal epithelial cell development columnar/cuboidal epithelial cell differentiation multicellular organismal process ossification osteoblast differentiation granulocyte differentiation neutrophil differentiation thioester biosynthetic process fatty-acyl-CoA biosynthetic process nucleobase-containing compound metabolic process acyl-CoA metabolic process nucleobase-containing small molecule metabolic process purine-containing compound biosynthetic process acyl-CoA biosynthetic process phosphate-containing compound metabolic process sulfur compound metabolic process amide metabolic process thioester metabolic process fatty-acyl-CoA metabolic process phosphorus metabolic process nucleoside phosphate metabolic process fatty acid derivative biosynthetic process amide biosynthetic process nucleobase-containing compound biosynthetic process fatty acid derivative metabolic process purine-containing compound metabolic process sulfur compound biosynthetic process organophosphate metabolic process organophosphate biosynthetic process nucleoside phosphate biosynthetic process modulation by host of viral process biological process involved in interspecies interaction between organisms modulation of process of another organism host-mediated perturbation of symbiont process fatty acid metabolic process oxoacid metabolic process carboxylic acid metabolic process monocarboxylic acid metabolic process organic acid metabolic process monocarboxylic acid biosynthetic process small molecule biosynthetic process organic acid biosynthetic process fatty acid biosynthetic process carboxylic acid biosynthetic process defense response response to stress inflammatory response	cellular anatomical structure membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol cellular anatomical structure membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol glycogen granule intracellular organelle Golgi apparatus intracellular membrane-bounded organelle endomembrane system pigment granule intracellular vesicle melanosome cytoplasmic vesicle cell periphery plasma membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR016035	Acyl transferase/acyl hydrolase/lysophospholipase	Homologous Superfamily
A, B, C, D	IPR013217	Methyltransferase type 12	Domain
A, B, C, D	IPR020807	Polyketide synthase, dehydratase domain	Domain
A, B, C, D	IPR049552	Polyketide synthase, dehydratase domain, N-terminal	Domain
A, B, C, D	IPR016036	Malonyl-CoA ACP transacylase, ACP-binding	Homologous Superfamily
A, B, C, D	IPR014043	Acyl transferase domain	Domain
A, B, C, D	IPR032821	Polyketide synthase, C-terminal extension	Domain
A, B, C, D	IPR011032	GroES-like superfamily	Homologous Superfamily
A, B, C, D	IPR009081	Phosphopantetheine binding ACP domain	Domain
A, B, C, D	IPR016039	Thiolase-like	Homologous Superfamily
A, B, C, D	IPR001227	Acyl transferase domain superfamily	Homologous Superfamily
A, B, C, D	IPR036291	NAD(P)-binding domain superfamily	Homologous Superfamily
A, B, C, D	IPR018201	Beta-ketoacyl synthase, active site	Active Site
A, B, C, D	IPR014030	Beta-ketoacyl synthase-like, N-terminal	Domain
A, B, C, D	IPR001031	Thioesterase	Domain
A, B, C, D	IPR014031	Beta-ketoacyl synthase, C-terminal	Domain
A, B, C, D	IPR006162	Phosphopantetheine attachment site	PTM
A, B, C, D	IPR049391	Fatty acid synthase, pseudo-KR domain	Domain
A, B, C, D	IPR020843	Polyketide synthase, enoylreductase domain	Domain
A, B, C, D	IPR013968	Polyketide synthase, ketoreductase domain	Domain
A, B, C, D	IPR050091	Polyketide and Nonribosomal Peptide Biosynthesis Enzymes	Family
A, B, C, D	IPR020841	Polyketide synthase, beta-ketoacyl synthase domain	Domain
A, B, C, D	IPR036736	ACP-like superfamily	Homologous Superfamily
A, B, C, D	IPR020806	Polyketide synthase-like, phosphopantetheine-binding domain	Domain
A, B, C, D	IPR029063	S-adenosyl-L-methionine-dependent methyltransferase superfamily	Homologous Superfamily
A, B, C, D	IPR029058	Alpha/Beta hydrolase fold	Homologous Superfamily
A, B, C, D	IPR013149	Alcohol dehydrogenase-like, C-terminal	Domain
A, B, C, D	IPR042104	Polyketide synthase, dehydratase domain superfamily	Homologous Superfamily
A, B, C, D	IPR049900	Polyketide/metazoan fatty acid synthase, dehydratase domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: P49327	liposarcoma obesity disorder intellectual disability melanoma acute coronary syndrome breast carcinoma dilated cardiomyopathy hypertrophic cardiomyopathy cancer chronic kidney disease esophageal squamous cell carcinoma pleomorphic liposarcoma breast cancer congestive heart failure drug-induced liver injury liposarcoma obesity disorder intellectual disability melanoma acute coronary syndrome breast carcinoma dilated cardiomyopathy hypertrophic cardiomyopathy cancer chronic kidney disease esophageal squamous cell carcinoma pleomorphic liposarcoma breast cancer congestive heart failure drug-induced liver injury osteosarcoma glioblastoma pancreatic ductal adenocarcinoma Heart Failure, Right-Sided hepatocellular carcinoma type 2 diabetes mellitus interstitial cystitis atypical teratoid rhabdoid tumor malignant glioma cutaneous melanoma myopathy Emery-Dreifuss muscular dystrophy ovarian cancer pituitary cancer psoriasis ulcerative colitis large cell medulloblastoma benign neoplasm Dedifferentiated liposarcoma dilated cardiomyopathy 1A oligodendroglioma ovarian neoplasm heart failure subependymal giant cell astrocytoma attention deficit hyperactivity disorder, inattentive type lung adenocarcinoma non-alcoholic fatty liver disease