6LPT

Crystal structure of human D-2-hydroxyglutarate dehydrogenase in complex with D-lactate (D-LAC)

External Resource: Annotation

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

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	FAD-oxidase_C	e6lptA2	A: a+b two layers	X: Alpha-beta plaits	H: FAD-linked oxidases, C-terminal domain (From Topology)	T: FAD-linked oxidases, C-terminal domain	F: FAD-oxidase_C	ECOD (1.6)
A	FAD_binding_4	e6lptA1	A: a+b complex topology	X: FAD-binding domain-like	H: FAD-binding domain (From Topology)	T: FAD-binding domain	F: FAD_binding_4	ECOD (1.6)
B	FAD-oxidase_C	e6lptB1	A: a+b two layers	X: Alpha-beta plaits	H: FAD-linked oxidases, C-terminal domain (From Topology)	T: FAD-linked oxidases, C-terminal domain	F: FAD-oxidase_C	ECOD (1.6)
B	FAD_binding_4	e6lptB2	A: a+b complex topology	X: FAD-binding domain-like	H: FAD-binding domain (From Topology)	T: FAD-binding domain	F: FAD_binding_4	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF02913	FAD linked oxidases, C-terminal domain (FAD-oxidase_C)	FAD linked oxidases, C-terminal domain	This domain has a ferredoxin-like fold.	Domain
A, B	PF01565	FAD binding domain (FAD_binding_4)	FAD binding domain	This family consists of various enzymes that use FAD as a co-factor, most of the enzymes are similar to oxygen oxidoreductase. One of the enzymes Vanillyl-alcohol oxidase (VAO) has a solved structure, the alignment includes the FAD binding site, call ...	This family consists of various enzymes that use FAD as a co-factor, most of the enzymes are similar to oxygen oxidoreductase. One of the enzymes Vanillyl-alcohol oxidase (VAO) has a solved structure, the alignment includes the FAD binding site, called the PP-loop, between residues 99-110 [1]. The FAD molecule is covalently bound in the known structure, however the residue that links to the FAD is not in the alignment. VAO catalyses the oxidation of a wide variety of substrates, ranging form aromatic amines to 4-alkylphenols. Other members of this family include D-lactate dehydrogenase, this enzyme catalyses the conversion of D-lactate to pyruvate using FAD as a co-factor; mitomycin radical oxidase, this enzyme oxidises the reduced form of mitomycins and is involved in mitomycin resistance. This family includes MurB an UDP-N-acetylenolpyruvoylglucosamine reductase enzyme EC:1.1.1.158. This enzyme is involved in the biosynthesis of peptidoglycan [2].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	D-2-hydroxyglutarate dehydrogenase, mitochondrial	FAD binding flavin adenine dinucleotide binding binding nucleoside phosphate binding ion binding organic cyclic compound binding anion binding nucleotide binding heterocyclic compound binding small molecule binding cation binding transition metal ion binding zinc ion binding metal ion binding FAD binding flavin adenine dinucleotide binding binding nucleoside phosphate binding ion binding organic cyclic compound binding anion binding nucleotide binding heterocyclic compound binding small molecule binding cation binding transition metal ion binding zinc ion binding metal ion binding oxidoreductase activity oxidoreductase activity, acting on CH-OH group of donors (R)-2-hydroxyglutarate dehydrogenase activity catalytic activity	response to stimulus response to metal ion response to chemical response to zinc ion response to manganese ion metabolic process primary metabolic process protein metabolic process macromolecule metabolic process oxoacid metabolic process malate metabolic process cellular metabolic process dicarboxylic acid metabolic process carboxylic acid metabolic process response to stimulus response to metal ion response to chemical response to zinc ion response to manganese ion metabolic process primary metabolic process protein metabolic process macromolecule metabolic process oxoacid metabolic process malate metabolic process cellular metabolic process dicarboxylic acid metabolic process carboxylic acid metabolic process small molecule metabolic process cellular process organic acid metabolic process 2-oxoglutarate metabolic process response to cobalt ion	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle membrane-enclosed lumen mitochondrial matrix intracellular organelle lumen organelle lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR016167	FAD-binding, type PCMH, subdomain 1	Homologous Superfamily
A, B	IPR016164	FAD-linked oxidase-like, C-terminal	Homologous Superfamily
A, B	IPR051264	FAD-binding Oxidoreductase/Transferase Type 4	Family
A, B	IPR006094	FAD linked oxidase, N-terminal	Domain
A, B	IPR004113	FAD-binding oxidoreductase/transferase, type 4, C-terminal	Domain
A, B	IPR016166	FAD-binding domain, PCMH-type	Domain
A, B	IPR016171	Vanillyl-alcohol oxidase, C-terminal subdomain 2	Homologous Superfamily
A, B	IPR036318	FAD-binding, type PCMH-like superfamily	Homologous Superfamily
A, B	IPR016169	FAD-binding, type PCMH, subdomain 2	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: Q8N465	2-hydroxyglutaric aciduria D-2-hydroxyglutaric aciduria 1 D-2-hydroxyglutaric aciduria Amino Acid Metabolism, Inherited Disorders breast cancer inherited amino acid metabolic disorder large cell medulloblastoma ovarian cancer allergic rhinitis asthma Crohn disease intellectual disability leukodystrophy pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia brain glioma 2-hydroxyglutaric aciduria D-2-hydroxyglutaric aciduria 1 D-2-hydroxyglutaric aciduria Amino Acid Metabolism, Inherited Disorders breast cancer inherited amino acid metabolic disorder large cell medulloblastoma ovarian cancer allergic rhinitis asthma Crohn disease intellectual disability leukodystrophy pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia brain glioma inborn errors of metabolism L-2-hydroxyglutaric aciduria osteosarcoma

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.