2HDH

BIOCHEMICAL CHARACTERIZATION AND STRUCTURE DETERMINATION OF HUMAN HEART SHORT CHAIN L-3-HYDROXYACYL COA DEHYDROGENASE PROVIDE INSIGHT INTO CATALYTIC MECHANISM

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
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
Structure Motif: Primary M-CSA Annotation

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d2hdhb1	All alpha proteins	6-phosphogluconate dehydrogenase C-terminal domain-like	6-phosphogluconate dehydrogenase C-terminal domain-like	HCDH C-domain-like	Short chain L-3-hydroxyacyl CoA dehydrogenase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d2hdhb2	Alpha and beta proteins (a/b)	NAD(P)-binding Rossmann-fold domains	NAD(P)-binding Rossmann-fold domains	6-phosphogluconate dehydrogenase-like, N-terminal domain	Short chain L-3-hydroxyacyl CoA dehydrogenase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d2hdha1	All alpha proteins	6-phosphogluconate dehydrogenase C-terminal domain-like	6-phosphogluconate dehydrogenase C-terminal domain-like	HCDH C-domain-like	Short chain L-3-hydroxyacyl CoA dehydrogenase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d2hdha2	Alpha and beta proteins (a/b)	NAD(P)-binding Rossmann-fold domains	NAD(P)-binding Rossmann-fold domains	6-phosphogluconate dehydrogenase-like, N-terminal domain	Short chain L-3-hydroxyacyl CoA dehydrogenase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B	SCOP2B Superfamily	6-phosphogluconate dehydrogenase-like	8001136	3000048	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	6-phosphogluconate dehydrogenase-like	8001136	3000048	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)
B	3HCDH	e2hdhB1	A: alpha arrays	X: 6-phosphogluconate dehydrogenase C-terminal domain-like (From Topology)	H: 6-phosphogluconate dehydrogenase C-terminal domain-like (From Topology)	T: 6-phosphogluconate dehydrogenase C-terminal domain-like	F: 3HCDH	ECOD (1.6)
B	3HCDH_N	e2hdhB2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: 3HCDH_N	ECOD (1.6)
A	3HCDH	e2hdhA1	A: alpha arrays	X: 6-phosphogluconate dehydrogenase C-terminal domain-like (From Topology)	H: 6-phosphogluconate dehydrogenase C-terminal domain-like (From Topology)	T: 6-phosphogluconate dehydrogenase C-terminal domain-like	F: 3HCDH	ECOD (1.6)
A	3HCDH_N	e2hdhA2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: 3HCDH_N	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	3.40.50.720	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	NAD(P)-binding Rossmann-like Domain	CATH (4.3.0)
B	1.10.1040.10	Mainly Alpha	Orthogonal Bundle	N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase	domain 2	CATH (4.3.0)
A	3.40.50.720	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	NAD(P)-binding Rossmann-like Domain	CATH (4.3.0)
A	1.10.1040.10	Mainly Alpha	Orthogonal Bundle	N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase	domain 2	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF02737	3-hydroxyacyl-CoA dehydrogenase, NAD binding domain (3HCDH_N)	3-hydroxyacyl-CoA dehydrogenase, NAD binding domain	This family also includes lambda crystallin.	Domain
A, B	PF00725	3-hydroxyacyl-CoA dehydrogenase, C-terminal domain (3HCDH)	3-hydroxyacyl-CoA dehydrogenase, C-terminal domain	This family also includes lambda crystallin. Some proteins include two copies of this domain.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	L-3-HYDROXYACYL COA DEHYDROGENASE	NAD+ binding NAD binding binding nucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding heterocyclic compound binding small molecule binding oxidoreductase activity oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor NAD+ binding NAD binding binding nucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding heterocyclic compound binding small molecule binding 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 3-hydroxyacyl-CoA dehydrogenase activity catalytic activity transferase activity identical protein binding protein binding	response to stimulus response to chemical response to xenobiotic stimulus multicellular organismal process regulation of biological process regulation of cellular process homeostatic process biological regulation positive regulation of biological process adaptive thermogenesis positive regulation of metabolic process multicellular organismal-level homeostasis regulation of cold-induced thermogenesis cold-induced thermogenesis response to stimulus response to chemical response to xenobiotic stimulus multicellular organismal process regulation of biological process regulation of cellular process homeostatic process biological regulation positive regulation of biological process adaptive thermogenesis positive regulation of metabolic process multicellular organismal-level homeostasis regulation of cold-induced thermogenesis cold-induced thermogenesis temperature homeostasis positive regulation of cold-induced thermogenesis positive regulation of multicellular organismal process cellular process metabolic process regulation of multicellular organismal process regulation of metabolic process positive regulation of cellular process protein localization regulation of localization establishment of protein localization nitrogen compound transport cell communication localization cellular macromolecule localization regulation of biological quality regulation of peptide hormone secretion regulation of hormone levels establishment of protein localization to extracellular region protein secretion establishment of localization regulation of protein secretion regulation of secretion cellular localization regulation of hormone secretion regulation of protein localization regulation of peptide secretion transport signaling hormone secretion protein localization to extracellular region peptide secretion secretion by cell regulation of secretion by cell amide transport signal release regulation of signaling secretion regulation of transport regulation of peptide transport regulation of establishment of protein localization cell-cell signaling export from cell regulation of protein transport peptide transport protein transport regulation of cellular localization regulation of insulin secretion peptide hormone secretion macromolecule localization hormone transport regulation of cell communication insulin secretion response to hormone response to endogenous stimulus response to peptide hormone response to insulin response to oxygen-containing compound response to nitrogen compound fatty acid metabolic process lipid catabolic process catabolic process oxoacid metabolic process carboxylic acid metabolic process primary metabolic process lipid modification organic acid catabolic process organic acid metabolic process fatty acid catabolic process cellular catabolic process monocarboxylic acid catabolic process fatty acid oxidation carboxylic acid catabolic process fatty acid beta-oxidation small molecule metabolic process monocarboxylic acid metabolic process lipid oxidation small molecule catabolic process lipid metabolic process response to activity negative regulation of protein transport negative regulation of biological process negative regulation of transport negative regulation of secretion negative regulation of hormone secretion negative regulation of secretion by cell negative regulation of peptide hormone secretion negative regulation of establishment of protein localization negative regulation of protein secretion negative regulation of signaling negative regulation of cell communication negative regulation of peptide secretion negative regulation of cellular process negative regulation of protein localization negative regulation of insulin secretion	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen mitochondrial matrix

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR052242	Mitochondrial 3-hydroxyacyl-CoA dehydrogenase	Family
A, B	IPR008927	6-phosphogluconate dehydrogenase-like, C-terminal domain superfamily	Homologous Superfamily
A, B	IPR006108	3-hydroxyacyl-CoA dehydrogenase, C-terminal	Domain
A, B	IPR036291	NAD(P)-binding domain superfamily	Homologous Superfamily
A, B	IPR013328	6-phosphogluconate dehydrogenase, domain 2	Homologous Superfamily
A, B	IPR006180	3-hydroxyacyl-CoA dehydrogenase, conserved site	Conserved Site
A, B	IPR006176	3-hydroxyacyl-CoA dehydrogenase, NAD binding	Domain
A, B	IPR022694	3-hydroxyacyl-CoA dehydrogenase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: Q16836	hyperinsulinemic hypoglycemia, familial, 4 obesity disorder hyperinsulinemic hypoglycemia hyperinsulinism due to short chain 3-hydroxylacyl-CoA dehydrogenase deficiency medulloblastoma ovarian cancer precancerous condition ulcerative colitis 3-alpha-hydroxyacyl-CoA dehydrogenase deficiency arthrogryposis inborn errors of metabolism invasive ductal breast carcinoma malignant colon neoplasm myopathy pancreatic ductal adenocarcinoma hyperinsulinemic hypoglycemia, familial, 4 obesity disorder hyperinsulinemic hypoglycemia hyperinsulinism due to short chain 3-hydroxylacyl-CoA dehydrogenase deficiency medulloblastoma ovarian cancer precancerous condition ulcerative colitis 3-alpha-hydroxyacyl-CoA dehydrogenase deficiency arthrogryposis inborn errors of metabolism invasive ductal breast carcinoma malignant colon neoplasm myopathy pancreatic ductal adenocarcinoma 3-hydroxyacyl-CoA dehydrogenase deficiency astrocytic tumor ductal breast carcinoma in situ hyperinsulinism intellectual disability lung adenocarcinoma malignant ependymoma plasma cell myeloma rheumatoid arthritis acute myeloid leukemia B-cell chronic lymphocytic leukemia interstitial cystitis lymphoplasmacytic lymphoma

Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage

Chains	Enzyme Name	Description	Catalytic Residues
A	L-3-hydroxyacyl-CoA dehydrogenase M-CSA #336	L-3-hydroxyacyl-CoA dehydrogenase reversibly catalyses the conversion of L-3-hydroxyacyl-CoA to the 3-ketoyl acid derivative by proton abstraction and concurrent oxidation by the NAD+ cofactor, the penultimate step in the beta-oxidation spiral, and involved in fatty acid metabolism.	Defined by 4 residues: SER:A-126 [auth A-137]HIS:A-147 [auth A-158]GLU:A-159 [auth A-170]ASN:A-197 [auth A-208] \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 1.1.1.35 (PDB Primary Data) Search M-CSA Motif + EC 1.1.1.35

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.