Annotations: 1NI4

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d1ni4a1	Alpha and beta proteins (a/b)	Thiamin diphosphate-binding fold (THDP-binding)	Thiamin diphosphate-binding fold (THDP-binding)	Branched-chain alpha-keto acid dehydrogenase PP module	E1-beta subunit of pyruvate dehydrogenase (PP module)	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1ni4a2	Artifacts	Tags	Tags	Tags	N-terminal Tags	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d1ni4c1	Alpha and beta proteins (a/b)	Thiamin diphosphate-binding fold (THDP-binding)	Thiamin diphosphate-binding fold (THDP-binding)	Branched-chain alpha-keto acid dehydrogenase PP module	E1-beta subunit of pyruvate dehydrogenase (PP module)	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d1ni4c2	Artifacts	Tags	Tags	Tags	N-terminal Tags	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d1ni4b1	Alpha and beta proteins (a/b)	Thiamin diphosphate-binding fold (THDP-binding)	Thiamin diphosphate-binding fold (THDP-binding)	Branched-chain alpha-keto acid dehydrogenase Pyr module	E1-beta subunit of pyruvate dehydrogenase, Pyr module	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d1ni4b2	Alpha and beta proteins (a/b)	TK C-terminal domain-like	TK C-terminal domain-like	Branched-chain alpha-keto acid dehydrogenase beta-subunit, C-terminal-domain	E1-beta subunit of pyruvate dehydrogenase, C-domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d1ni4b3	Artifacts	Tags	Tags	Tags	N-terminal Tags	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d1ni4d1	Alpha and beta proteins (a/b)	Thiamin diphosphate-binding fold (THDP-binding)	Thiamin diphosphate-binding fold (THDP-binding)	Branched-chain alpha-keto acid dehydrogenase Pyr module	E1-beta subunit of pyruvate dehydrogenase, Pyr module	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d1ni4d2	Alpha and beta proteins (a/b)	TK C-terminal domain-like	TK C-terminal domain-like	Branched-chain alpha-keto acid dehydrogenase beta-subunit, C-terminal-domain	E1-beta subunit of pyruvate dehydrogenase, C-domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d1ni4d3	Artifacts	Tags	Tags	Tags	N-terminal Tags	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)
A	SCOP2 Family	Branched-chain alpha-keto acid dehydrogenase PP module	8020953	4003592	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Thiamin diphosphate-binding fold (THDP-binding)	8033333	3001790	SCOP2 (2022-06-29)
C	SCOP2B Superfamily	Thiamin diphosphate-binding fold (THDP-binding)	8033333	3001790	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	TK C-terminal domain-like	8043741	3000424	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Thiamin diphosphate-binding fold (THDP-binding)	8043740	3001790	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Thiamin diphosphate-binding fold (THDP-binding)	8043740	3001790	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	TK C-terminal domain-like	8043741	3000424	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	PF00676	e1ni4A1	A: a/b three-layered sandwiches	X: Thiamin diphosphate-binding fold (THDP-binding) (From Topology)	H: Thiamin diphosphate-binding fold (THDP-binding) (From Topology)	T: Thiamin diphosphate-binding fold (THDP-binding)	F: PF00676	ECOD (1.6)
C	PF00676	e1ni4C1	A: a/b three-layered sandwiches	X: Thiamin diphosphate-binding fold (THDP-binding) (From Topology)	H: Thiamin diphosphate-binding fold (THDP-binding) (From Topology)	T: Thiamin diphosphate-binding fold (THDP-binding)	F: PF00676	ECOD (1.6)
B	PF02780	e1ni4B1	A: a/b three-layered sandwiches	X: TK C-terminal domain-like (From Topology)	H: TK C-terminal domain-like (From Topology)	T: TK C-terminal domain-like	F: PF02780	ECOD (1.6)
B	PF02779	e1ni4B2	A: a/b three-layered sandwiches	X: Thiamin diphosphate-binding fold (THDP-binding) (From Topology)	H: Thiamin diphosphate-binding fold (THDP-binding) (From Topology)	T: Thiamin diphosphate-binding fold (THDP-binding)	F: PF02779	ECOD (1.6)
D	PF02780	e1ni4D1	A: a/b three-layered sandwiches	X: TK C-terminal domain-like (From Topology)	H: TK C-terminal domain-like (From Topology)	T: TK C-terminal domain-like	F: PF02780	ECOD (1.6)
D	PF02779	e1ni4D2	A: a/b three-layered sandwiches	X: Thiamin diphosphate-binding fold (THDP-binding) (From Topology)	H: Thiamin diphosphate-binding fold (THDP-binding) (From Topology)	T: Thiamin diphosphate-binding fold (THDP-binding)	F: PF02779	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.50.970	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Thiamin diphosphate (ThDP)-binding fold, Pyr/PP domains	CATH (4.3.0)
C	3.40.50.970	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Thiamin diphosphate (ThDP)-binding fold, Pyr/PP domains	CATH (4.3.0)
B	3.40.50.970	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Thiamin diphosphate (ThDP)-binding fold, Pyr/PP domains	CATH (4.3.0)
B	3.40.50.920	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold		CATH (4.3.0)
D	3.40.50.970	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Thiamin diphosphate (ThDP)-binding fold, Pyr/PP domains	CATH (4.3.0)
D	3.40.50.920	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold		CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, C	PF00676	Dehydrogenase E1 component (E1_dh)	Dehydrogenase E1 component	-	Family
B, D	PF02779	Transketolase, pyrimidine binding domain (Transket_pyr)	Transketolase, pyrimidine binding domain	This family includes transketolase enzymes, pyruvate dehydrogenases, and branched chain alpha-keto acid decarboxylases.	Domain
B, D	PF02780	Transketolase, C-terminal domain (Transketolase_C)	Transketolase, C-terminal domain	The C-terminal domain of transketolase has been proposed as a regulatory molecule binding site [2].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, C	Pyruvate dehydrogenase E1 component: Alpha subunit	oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor oxidoreductase activity pyruvate dehydrogenase (acetyl-transferring) activity oxidoreductase activity, acting on the aldehyde or oxo group of donors pyruvate dehydrogenase activity catalytic activity pyruvate dehydrogenase [NAD(P)+] activity pyruvate dehydrogenase (NAD+) activity oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor	aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds cellular metabolic process metabolic process cellular process primary metabolic process generation of precursor metabolites and energy nucleoside bisphosphate metabolic process ribonucleoside bisphosphate biosynthetic process oxoacid metabolic process nucleotide biosynthetic process organonitrogen compound biosynthetic process aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds cellular metabolic process metabolic process cellular process primary metabolic process generation of precursor metabolites and energy nucleoside bisphosphate metabolic process ribonucleoside bisphosphate biosynthetic process oxoacid metabolic process nucleotide biosynthetic process organonitrogen compound biosynthetic process carbohydrate derivative metabolic process purine ribonucleotide biosynthetic process acetyl-CoA metabolic process organic acid metabolic process nucleobase-containing compound metabolic process ribonucleotide biosynthetic process phosphate-containing compound metabolic process organic substance biosynthetic process small molecule metabolic process sulfur compound metabolic process thioester metabolic process phosphorus metabolic process ribose phosphate biosynthetic process nucleoside phosphate metabolic process pyruvate metabolic process amide biosynthetic process nucleotide metabolic process organic cyclic compound metabolic process sulfur compound biosynthetic process biosynthetic process organophosphate biosynthetic process organic cyclic compound biosynthetic process nucleoside phosphate biosynthetic process monocarboxylic acid metabolic process purine ribonucleotide metabolic process purine nucleotide biosynthetic process ribose phosphate metabolic process purine nucleoside bisphosphate metabolic process ribonucleoside bisphosphate metabolic process acetyl-CoA biosynthetic process from pyruvate thioester biosynthetic process cellular biosynthetic process purine nucleotide metabolic process organic substance metabolic process acyl-CoA metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine-containing compound biosynthetic process acyl-CoA biosynthetic process purine nucleoside bisphosphate biosynthetic process amide metabolic process carbohydrate derivative biosynthetic process organonitrogen compound metabolic process nucleoside bisphosphate biosynthetic process carboxylic acid metabolic process nucleobase-containing compound biosynthetic process purine-containing compound metabolic process acetyl-CoA biosynthetic process organophosphate metabolic process monosaccharide metabolic process carbohydrate metabolic process hexose metabolic process glucose metabolic process	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle protein-containing complex catalytic complex oxidoreductase complex pyruvate dehydrogenase complex alpha-ketoacid dehydrogenase complex nucleus membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle protein-containing complex catalytic complex oxidoreductase complex pyruvate dehydrogenase complex alpha-ketoacid dehydrogenase complex nucleus membrane-enclosed lumen nucleolus intracellular organelle lumen organelle lumen intracellular non-membrane-bounded organelle nuclear lumen non-membrane-bounded organelle mitochondrial matrix
B, D	Pyruvate dehydrogenase E1 component: Beta subunit	oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor oxidoreductase activity pyruvate dehydrogenase (acetyl-transferring) activity oxidoreductase activity, acting on the aldehyde or oxo group of donors pyruvate dehydrogenase activity catalytic activity	aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds cellular metabolic process metabolic process cellular process primary metabolic process generation of precursor metabolites and energy nucleoside bisphosphate metabolic process ribonucleoside bisphosphate biosynthetic process oxoacid metabolic process nucleotide biosynthetic process organonitrogen compound biosynthetic process aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds cellular metabolic process metabolic process cellular process primary metabolic process generation of precursor metabolites and energy nucleoside bisphosphate metabolic process ribonucleoside bisphosphate biosynthetic process oxoacid metabolic process nucleotide biosynthetic process organonitrogen compound biosynthetic process carbohydrate derivative metabolic process purine ribonucleotide biosynthetic process acetyl-CoA metabolic process organic acid metabolic process nucleobase-containing compound metabolic process ribonucleotide biosynthetic process phosphate-containing compound metabolic process organic substance biosynthetic process small molecule metabolic process sulfur compound metabolic process thioester metabolic process phosphorus metabolic process ribose phosphate biosynthetic process nucleoside phosphate metabolic process pyruvate metabolic process amide biosynthetic process nucleotide metabolic process organic cyclic compound metabolic process sulfur compound biosynthetic process biosynthetic process organophosphate biosynthetic process organic cyclic compound biosynthetic process nucleoside phosphate biosynthetic process monocarboxylic acid metabolic process purine ribonucleotide metabolic process purine nucleotide biosynthetic process ribose phosphate metabolic process purine nucleoside bisphosphate metabolic process ribonucleoside bisphosphate metabolic process acetyl-CoA biosynthetic process from pyruvate thioester biosynthetic process cellular biosynthetic process purine nucleotide metabolic process organic substance metabolic process acyl-CoA metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine-containing compound biosynthetic process acyl-CoA biosynthetic process purine nucleoside bisphosphate biosynthetic process amide metabolic process carbohydrate derivative biosynthetic process organonitrogen compound metabolic process nucleoside bisphosphate biosynthetic process carboxylic acid metabolic process nucleobase-containing compound biosynthetic process purine-containing compound metabolic process acetyl-CoA biosynthetic process organophosphate metabolic process monosaccharide metabolic process carbohydrate metabolic process hexose metabolic process glucose metabolic process	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle protein-containing complex catalytic complex oxidoreductase complex pyruvate dehydrogenase complex alpha-ketoacid dehydrogenase complex nucleus membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle protein-containing complex catalytic complex oxidoreductase complex pyruvate dehydrogenase complex alpha-ketoacid dehydrogenase complex 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, C	IPR029061	Thiamin diphosphate-binding fold	Homologous Superfamily
A, C	IPR017597	Pyruvate dehydrogenase (acetyl-transferring) E1 component, alpha subunit, subgroup y	Family
A, C	IPR001017	Dehydrogenase, E1 component	Domain
B, D	IPR029061	Thiamin diphosphate-binding fold	Homologous Superfamily
B, D	IPR009014	Transketolase C-terminal/Pyruvate-ferredoxin oxidoreductase domain II	Homologous Superfamily
B, D	IPR005475	Transketolase-like, pyrimidine-binding domain	Domain
B, D	IPR027110	Pyruvate dehydrogenase E1 component subunit beta	Family
B, D	IPR033248	Transketolase, C-terminal domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, C	Pharos: P08559	pyruvate dehydrogenase deficiency Leigh syndrome prostate cancer pyruvate dehydrogenase E1-alpha deficiency Pyruvate Metabolism, Inborn Errors osteoarthritis osteosarcoma Pick disease acquired lactic acidosis Charcot-Marie-Tooth disease gastric cancer hereditary diffuse gastric adenocarcinoma invasive ductal breast carcinoma myocardial ischemia osteoarthritis susceptibility 1 pyruvate dehydrogenase deficiency Leigh syndrome prostate cancer pyruvate dehydrogenase E1-alpha deficiency Pyruvate Metabolism, Inborn Errors osteoarthritis osteosarcoma Pick disease acquired lactic acidosis Charcot-Marie-Tooth disease gastric cancer hereditary diffuse gastric adenocarcinoma invasive ductal breast carcinoma myocardial ischemia osteoarthritis susceptibility 1 ovarian cancer plasma cell myeloma astrocytic tumor coronary artery disease ductal breast carcinoma in situ gastric neoplasm inborn errors of metabolism myopathy pancreatic intraductal papillary-mucinous neoplasm glioblastoma intellectual disability lactic acidosis
B, D	Pharos: P11177	pyruvate dehydrogenase E1-beta deficiency renal cell carcinoma pyruvate dehydrogenase deficiency collecting duct carcinoma sarcomatoid renal cell carcinoma chromophobe renal cell carcinoma Leigh syndrome papillary renal cell carcinoma systemic sclerosis Ataxia with Lactic Acidosis, Type I lung carcinoma pancreatic ductal adenocarcinoma renal carcinoma systemic lupus erythematosus clear cell renal carcinoma pyruvate dehydrogenase E1-beta deficiency renal cell carcinoma pyruvate dehydrogenase deficiency collecting duct carcinoma sarcomatoid renal cell carcinoma chromophobe renal cell carcinoma Leigh syndrome papillary renal cell carcinoma systemic sclerosis Ataxia with Lactic Acidosis, Type I lung carcinoma pancreatic ductal adenocarcinoma renal carcinoma systemic lupus erythematosus clear cell renal carcinoma inborn errors of metabolism lung cancer ovarian cancer plasma cell myeloma

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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 R01GM133198.