6CER | pdb_00006cer

Human pyruvate dehydrogenase complex E1 component V138M mutation

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

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d6cerb1	Alpha and beta proteins (a/b)	Thiamin diphosphate-binding fold (THDP-binding)	Thiamin diphosphate-binding fold (THDP-binding)	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d6cerb2	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	d6cerb3	Artifacts	Tags	Tags	Tags	N-terminal Tags	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d6cerd1	Alpha and beta proteins (a/b)	Thiamin diphosphate-binding fold (THDP-binding)	Thiamin diphosphate-binding fold (THDP-binding)	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d6cerd2	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	d6cerd3	Artifacts	Tags	Tags	Tags	N-terminal Tags	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
F	d6cerf1	Alpha and beta proteins (a/b)	Thiamin diphosphate-binding fold (THDP-binding)	Thiamin diphosphate-binding fold (THDP-binding)	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
F	d6cerf2	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)
F	d6cerf3	Artifacts	Tags	Tags	Tags	N-terminal Tags	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
H	d6cerh1	Alpha and beta proteins (a/b)	Thiamin diphosphate-binding fold (THDP-binding)	Thiamin diphosphate-binding fold (THDP-binding)	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
H	d6cerh2	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)
H	d6cerh3	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	SCOP2B Superfamily	Thiamin diphosphate-binding fold (THDP-binding)	8033333	3001790	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Thiamin diphosphate-binding fold (THDP-binding)	8033333	3001790	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Thiamin diphosphate-binding fold (THDP-binding)	8033333	3001790	SCOP2B (2022-06-29)
G	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	TK C-terminal domain-like	8043741	3000424	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Thiamin diphosphate-binding fold (THDP-binding)	8043740	3001790	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Thiamin diphosphate-binding fold (THDP-binding)	8043740	3001790	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	TK C-terminal domain-like	8043741	3000424	SCOP2B (2022-06-29)
H	SCOP2B Superfamily	TK C-terminal domain-like	8043741	3000424	SCOP2B (2022-06-29)
H	SCOP2B Superfamily	Thiamin diphosphate-binding fold (THDP-binding)	8043740	3001790	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	E1_dh	e6cerA1	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: E1_dh	ECOD (1.6)
C	E1_dh	e6cerC1	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: E1_dh	ECOD (1.6)
E	E1_dh	e6cerE1	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: E1_dh	ECOD (1.6)
G	E1_dh	e6cerG1	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: E1_dh	ECOD (1.6)
B	Transketolase_C	e6cerB1	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: Transketolase_C	ECOD (1.6)
B	Transket_pyr	e6cerB2	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: Transket_pyr	ECOD (1.6)
D	Transketolase_C	e6cerD2	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: Transketolase_C	ECOD (1.6)
D	Transket_pyr	e6cerD1	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: Transket_pyr	ECOD (1.6)
F	Transketolase_C	e6cerF2	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: Transketolase_C	ECOD (1.6)
F	Transket_pyr	e6cerF1	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: Transket_pyr	ECOD (1.6)
H	Transketolase_C	e6cerH1	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: Transketolase_C	ECOD (1.6)
H	Transket_pyr	e6cerH2	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: Transket_pyr	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)
E	3.40.50.970	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Thiamin diphosphate (ThDP)-binding fold, Pyr/PP domains	CATH (4.3.0)
G	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)
F	3.40.50.970	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Thiamin diphosphate (ThDP)-binding fold, Pyr/PP domains	CATH (4.3.0)
F	3.40.50.920	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold		CATH (4.3.0)
H	3.40.50.970	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Thiamin diphosphate (ThDP)-binding fold, Pyr/PP domains	CATH (4.3.0)
H	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, E, G	PF00676	Dehydrogenase E1 component (E1_dh)	Dehydrogenase E1 component	This family uses thiamine pyrophosphate as a cofactor. This family includes pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase and 2-oxoisovalerate dehydrogenase.	Domain
B, D, F, H	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, F, H	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, E, G	Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial	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 cation binding ion binding binding metal ion binding small molecule binding	aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds primary metabolic process metabolic process cellular process generation of precursor metabolites and energy oxoacid metabolic process thioester biosynthetic process acetyl-CoA metabolic process organic acid metabolic process nucleobase-containing compound metabolic process acyl-CoA metabolic process aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds primary metabolic process metabolic process cellular process generation of precursor metabolites and energy oxoacid metabolic process thioester biosynthetic process acetyl-CoA metabolic process organic acid metabolic 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 small molecule metabolic process amide metabolic process thioester metabolic process phosphorus metabolic process nucleoside phosphate metabolic process pyruvate metabolic process carboxylic acid metabolic process pyruvate decarboxylation to acetyl-CoA amide biosynthetic process nucleobase-containing compound biosynthetic process purine-containing compound metabolic process acetyl-CoA biosynthetic process sulfur compound biosynthetic process biosynthetic process organophosphate metabolic process organophosphate biosynthetic process nucleoside phosphate biosynthetic process monocarboxylic acid metabolic process monosaccharide metabolic process carbohydrate metabolic process hexose metabolic process glucose metabolic process	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle protein-containing complex catalytic complex oxidoreductase complex pyruvate dehydrogenase complex alpha-ketoacid dehydrogenase complex nucleus membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle protein-containing complex catalytic complex oxidoreductase complex pyruvate dehydrogenase complex alpha-ketoacid dehydrogenase complex nucleus membrane-enclosed lumen intracellular membraneless organelle nucleolus intracellular organelle lumen organelle lumen membraneless organelle nuclear lumen mitochondrial matrix
B, D, F, H	Pyruvate dehydrogenase E1 component subunit beta, mitochondrial	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 cation binding ion binding binding metal ion binding small molecule binding	aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds primary metabolic process metabolic process cellular process generation of precursor metabolites and energy oxoacid metabolic process thioester biosynthetic process acetyl-CoA metabolic process organic acid metabolic process nucleobase-containing compound metabolic process acyl-CoA metabolic process aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds primary metabolic process metabolic process cellular process generation of precursor metabolites and energy oxoacid metabolic process thioester biosynthetic process acetyl-CoA metabolic process organic acid metabolic 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 small molecule metabolic process amide metabolic process thioester metabolic process phosphorus metabolic process nucleoside phosphate metabolic process pyruvate metabolic process carboxylic acid metabolic process pyruvate decarboxylation to acetyl-CoA amide biosynthetic process nucleobase-containing compound biosynthetic process purine-containing compound metabolic process acetyl-CoA biosynthetic process sulfur compound biosynthetic process biosynthetic process organophosphate metabolic process organophosphate biosynthetic process nucleoside phosphate biosynthetic process monocarboxylic acid metabolic process monosaccharide metabolic process carbohydrate metabolic process hexose metabolic process glucose metabolic process	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle protein-containing complex catalytic complex oxidoreductase complex pyruvate dehydrogenase complex alpha-ketoacid dehydrogenase complex nucleus membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm 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, E, G	IPR050642	Pyruvate Dehydrogenase E1 Alpha Subunit	Family
A, C, E, G	IPR029061	Thiamin diphosphate-binding fold	Homologous Superfamily
A, C, E, G	IPR017597	Pyruvate dehydrogenase (acetyl-transferring) E1 component, alpha subunit, subgroup y	Family
A, C, E, G	IPR001017	Dehydrogenase, E1 component	Domain
B, D, F, H	IPR029061	Thiamin diphosphate-binding fold	Homologous Superfamily
B, D, F, H	IPR009014	Transketolase C-terminal/Pyruvate-ferredoxin oxidoreductase domain II	Homologous Superfamily
B, D, F, H	IPR027110	Pyruvate dehydrogenase E1 component subunit beta, mitochondrial-type	Family
B, D, F, H	IPR005475	Transketolase-like, pyrimidine-binding domain	Domain
B, D, F, H	IPR033248	Transketolase, C-terminal domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, C, E, G	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, F, H	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 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.