1H7X

Dihydropyrimidine dehydrogenase (DPD) from pig, ternary complex of a mutant enzyme (C671A), NADPH and 5-fluorouracil

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
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)
A	d1h7xa1	All alpha proteins	Globin-like	alpha-helical ferredoxin	Dihydropyrimidine dehydrogenase, N-terminal domain	Dihydropyrimidine dehydrogenase, N-terminal domain	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
A	d1h7xa2	Alpha and beta proteins (a/b)	TIM beta/alpha-barrel	FMN-linked oxidoreductases	FMN-linked oxidoreductases	Dihydropyrimidine dehydrogenase, domain 4	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
A	d1h7xa3	Alpha and beta proteins (a/b)	FAD/NAD(P)-binding domain	FAD/NAD(P)-binding domain	C-terminal domain of adrenodoxin reductase-like	Dihydropyrimidine dehydrogenase, domain 3	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
A	d1h7xa4	Alpha and beta proteins (a/b)	Nucleotide-binding domain	Nucleotide-binding domain	N-terminal domain of adrenodoxin reductase-like	Dihydropyrimidine dehydrogenase, domain 2	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
A	d1h7xa5	Alpha and beta proteins (a+b)	Ferredoxin-like	4Fe-4S ferredoxins	Ferredoxin domains from multidomain proteins	Dihydropyrimidine dehydrogenase, C-terminal domain	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
D	d1h7xd1	All alpha proteins	Globin-like	alpha-helical ferredoxin	Dihydropyrimidine dehydrogenase, N-terminal domain	Dihydropyrimidine dehydrogenase, N-terminal domain	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
D	d1h7xd2	Alpha and beta proteins (a/b)	TIM beta/alpha-barrel	FMN-linked oxidoreductases	FMN-linked oxidoreductases	Dihydropyrimidine dehydrogenase, domain 4	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
D	d1h7xd3	Alpha and beta proteins (a/b)	FAD/NAD(P)-binding domain	FAD/NAD(P)-binding domain	C-terminal domain of adrenodoxin reductase-like	Dihydropyrimidine dehydrogenase, domain 3	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
D	d1h7xd4	Alpha and beta proteins (a/b)	Nucleotide-binding domain	Nucleotide-binding domain	N-terminal domain of adrenodoxin reductase-like	Dihydropyrimidine dehydrogenase, domain 2	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
D	d1h7xd5	Alpha and beta proteins (a+b)	Ferredoxin-like	4Fe-4S ferredoxins	Ferredoxin domains from multidomain proteins	Dihydropyrimidine dehydrogenase, C-terminal domain	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
B	d1h7xb1	All alpha proteins	Globin-like	alpha-helical ferredoxin	Dihydropyrimidine dehydrogenase, N-terminal domain	Dihydropyrimidine dehydrogenase, N-terminal domain	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
B	d1h7xb2	Alpha and beta proteins (a/b)	TIM beta/alpha-barrel	FMN-linked oxidoreductases	FMN-linked oxidoreductases	Dihydropyrimidine dehydrogenase, domain 4	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
B	d1h7xb3	Alpha and beta proteins (a/b)	FAD/NAD(P)-binding domain	FAD/NAD(P)-binding domain	C-terminal domain of adrenodoxin reductase-like	Dihydropyrimidine dehydrogenase, domain 3	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
B	d1h7xb4	Alpha and beta proteins (a/b)	Nucleotide-binding domain	Nucleotide-binding domain	N-terminal domain of adrenodoxin reductase-like	Dihydropyrimidine dehydrogenase, domain 2	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
B	d1h7xb5	Alpha and beta proteins (a+b)	Ferredoxin-like	4Fe-4S ferredoxins	Ferredoxin domains from multidomain proteins	Dihydropyrimidine dehydrogenase, C-terminal domain	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
C	d1h7xc1	All alpha proteins	Globin-like	alpha-helical ferredoxin	Dihydropyrimidine dehydrogenase, N-terminal domain	Dihydropyrimidine dehydrogenase, N-terminal domain	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
C	d1h7xc2	Alpha and beta proteins (a/b)	TIM beta/alpha-barrel	FMN-linked oxidoreductases	FMN-linked oxidoreductases	Dihydropyrimidine dehydrogenase, domain 4	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
C	d1h7xc3	Alpha and beta proteins (a/b)	FAD/NAD(P)-binding domain	FAD/NAD(P)-binding domain	C-terminal domain of adrenodoxin reductase-like	Dihydropyrimidine dehydrogenase, domain 3	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
C	d1h7xc4	Alpha and beta proteins (a/b)	Nucleotide-binding domain	Nucleotide-binding domain	N-terminal domain of adrenodoxin reductase-like	Dihydropyrimidine dehydrogenase, domain 2	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)
C	d1h7xc5	Alpha and beta proteins (a+b)	Ferredoxin-like	4Fe-4S ferredoxins	Ferredoxin domains from multidomain proteins	Dihydropyrimidine dehydrogenase, C-terminal domain	WILD BOAR (Sus scrofa ) [TaxId: 9823 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Thioredoxin reductase-like	8017506	3000050	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	FMN-linked oxidoreductases	8001523	3000014	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	4Fe-4S ferredoxins	8001525	3000020	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	alpha-helical ferredoxin	8001521	3000026	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	alpha-helical ferredoxin	8001521	3000026	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	FMN-linked oxidoreductases	8001523	3000014	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	4Fe-4S ferredoxins	8001525	3000020	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Thioredoxin reductase-like	8017506	3000050	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Thioredoxin reductase-like	8017506	3000050	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	alpha-helical ferredoxin	8001521	3000026	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	FMN-linked oxidoreductases	8001523	3000014	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	4Fe-4S ferredoxins	8001525	3000020	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	4Fe-4S ferredoxins	8001525	3000020	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	alpha-helical ferredoxin	8001521	3000026	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	FMN-linked oxidoreductases	8001523	3000014	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Thioredoxin reductase-like	8017506	3000050	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	Fer4_20	e1h7xA1	A: alpha arrays	X: alpha-helical ferredoxin-like	H: alpha-helical ferredoxin (From Topology)	T: alpha-helical ferredoxin	F: Fer4_20	ECOD (1.6)
A	Fer4_21	e1h7xA2	A: a+b two layers	X: 4Fe-4S ferredoxin (From Topology)	H: 4Fe-4S ferredoxin (From Topology)	T: 4Fe-4S ferredoxin	F: Fer4_21	ECOD (1.6)
A	DHO_dh	e1h7xA3	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: DHO_dh	ECOD (1.6)
A	Pyr_redox_2_3	e1h7xA4	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: FAD/NAD(P)-binding domain	F: Pyr_redox_2_3	ECOD (1.6)
A	Pyr_redox_2	e1h7xA5	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: Nucleotide-binding domain	F: Pyr_redox_2	ECOD (1.6)
D	Fer4_20	e1h7xD1	A: alpha arrays	X: alpha-helical ferredoxin-like	H: alpha-helical ferredoxin (From Topology)	T: alpha-helical ferredoxin	F: Fer4_20	ECOD (1.6)
D	Fer4_21	e1h7xD2	A: a+b two layers	X: 4Fe-4S ferredoxin (From Topology)	H: 4Fe-4S ferredoxin (From Topology)	T: 4Fe-4S ferredoxin	F: Fer4_21	ECOD (1.6)
D	DHO_dh	e1h7xD3	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: DHO_dh	ECOD (1.6)
D	Pyr_redox_2_3	e1h7xD4	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: FAD/NAD(P)-binding domain	F: Pyr_redox_2_3	ECOD (1.6)
D	Pyr_redox_2	e1h7xD5	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: Nucleotide-binding domain	F: Pyr_redox_2	ECOD (1.6)
B	Fer4_20	e1h7xB1	A: alpha arrays	X: alpha-helical ferredoxin-like	H: alpha-helical ferredoxin (From Topology)	T: alpha-helical ferredoxin	F: Fer4_20	ECOD (1.6)
B	Fer4_21	e1h7xB2	A: a+b two layers	X: 4Fe-4S ferredoxin (From Topology)	H: 4Fe-4S ferredoxin (From Topology)	T: 4Fe-4S ferredoxin	F: Fer4_21	ECOD (1.6)
B	DHO_dh	e1h7xB3	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: DHO_dh	ECOD (1.6)
B	Pyr_redox_2_3	e1h7xB4	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: FAD/NAD(P)-binding domain	F: Pyr_redox_2_3	ECOD (1.6)
B	Pyr_redox_2	e1h7xB5	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: Nucleotide-binding domain	F: Pyr_redox_2	ECOD (1.6)
C	Fer4_20	e1h7xC1	A: alpha arrays	X: alpha-helical ferredoxin-like	H: alpha-helical ferredoxin (From Topology)	T: alpha-helical ferredoxin	F: Fer4_20	ECOD (1.6)
C	Fer4_21	e1h7xC2	A: a+b two layers	X: 4Fe-4S ferredoxin (From Topology)	H: 4Fe-4S ferredoxin (From Topology)	T: 4Fe-4S ferredoxin	F: Fer4_21	ECOD (1.6)
C	DHO_dh	e1h7xC3	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: DHO_dh	ECOD (1.6)
C	Pyr_redox_2_3	e1h7xC4	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: FAD/NAD(P)-binding domain	F: Pyr_redox_2_3	ECOD (1.6)
C	Pyr_redox_2	e1h7xC5	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: Nucleotide-binding domain	F: Pyr_redox_2	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.70.20	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits		CATH (4.3.0)
A	1.10.1060.10	Mainly Alpha	Orthogonal Bundle	Fumarate Reductase Iron-sulfur Protein	Chain B, domain 2	CATH (4.3.0)
A	3.50.50.60	Alpha Beta	3-Layer(bba) Sandwich	FAD/NAD(P)-binding domain	FAD/NAD(P)-binding domain	CATH (4.3.0)
A	3.20.20.70	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Aldolase class I	CATH (4.3.0)
D	3.30.70.20	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits		CATH (4.3.0)
D	1.10.1060.10	Mainly Alpha	Orthogonal Bundle	Fumarate Reductase Iron-sulfur Protein	Chain B, domain 2	CATH (4.3.0)
D	3.50.50.60	Alpha Beta	3-Layer(bba) Sandwich	FAD/NAD(P)-binding domain	FAD/NAD(P)-binding domain	CATH (4.3.0)
D	3.20.20.70	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Aldolase class I	CATH (4.3.0)
B	3.30.70.20	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits		CATH (4.3.0)
B	1.10.1060.10	Mainly Alpha	Orthogonal Bundle	Fumarate Reductase Iron-sulfur Protein	Chain B, domain 2	CATH (4.3.0)
B	3.50.50.60	Alpha Beta	3-Layer(bba) Sandwich	FAD/NAD(P)-binding domain	FAD/NAD(P)-binding domain	CATH (4.3.0)
B	3.20.20.70	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Aldolase class I	CATH (4.3.0)
C	3.30.70.20	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits		CATH (4.3.0)
C	1.10.1060.10	Mainly Alpha	Orthogonal Bundle	Fumarate Reductase Iron-sulfur Protein	Chain B, domain 2	CATH (4.3.0)
C	3.50.50.60	Alpha Beta	3-Layer(bba) Sandwich	FAD/NAD(P)-binding domain	FAD/NAD(P)-binding domain	CATH (4.3.0)
C	3.20.20.70	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Aldolase class I	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF07992	Pyridine nucleotide-disulphide oxidoreductase (Pyr_redox_2)	Pyridine nucleotide-disulphide oxidoreductase	This family includes both class I and class II oxidoreductases and also NADH oxidases and peroxidases. This domain is actually a small NADH binding domain within a larger FAD binding domain.	Domain
A, B, C, D	PF01180	Dihydroorotate dehydrogenase (DHO_dh)	Dihydroorotate dehydrogenase	-	Domain
A, B, C, D	PF14691	Dihydroprymidine dehydrogenase domain II, 4Fe-4S cluster (Fer4_20)	Dihydroprymidine dehydrogenase domain II, 4Fe-4S cluster	Domain II of the enzyme dihydroprymidine dehydrogenase binds FAD. Dihydroprymidine dehydrogenase catalyses the first and rate-limiting step of pyrimidine degradation by converting pyrimidines to the corresponding 5,6- dihydro compounds [1]. This doma ...	Domain II of the enzyme dihydroprymidine dehydrogenase binds FAD. Dihydroprymidine dehydrogenase catalyses the first and rate-limiting step of pyrimidine degradation by converting pyrimidines to the corresponding 5,6- dihydro compounds [1]. This domain carries two Fe4-S4 clusters.	Domain
A, B, C, D	PF14697	4Fe-4S dicluster domain (Fer4_21)	4Fe-4S dicluster domain	Superfamily includes proteins containing domains which bind to iron-sulfur clusters. Members include bacterial ferredoxins, various dehydrogenases, and various reductases. Structure of the domain is an alpha-antiparallel beta sandwich. Domain contai ...	Superfamily includes proteins containing domains which bind to iron-sulfur clusters. Members include bacterial ferredoxins, various dehydrogenases, and various reductases. Structure of the domain is an alpha-antiparallel beta sandwich. Domain contains two 4Fe4S clusters.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	DIHYDROPYRIMIDINE DEHYDROGENASE	dihydropyrimidine dehydrogenase (NADP+) activity oxidoreductase activity 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 catalytic activity binding nucleotide binding FMN binding nucleoside phosphate binding ion binding organic cyclic compound binding anion binding heterocyclic compound binding carbohydrate derivative binding dihydropyrimidine dehydrogenase (NADP+) activity oxidoreductase activity 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 catalytic activity binding nucleotide binding FMN binding nucleoside phosphate binding ion binding organic cyclic compound binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding purine nucleotide binding adenyl nucleotide binding NADP binding identical protein binding protein binding protein homodimerization activity protein dimerization activity flavin adenine dinucleotide binding iron-sulfur cluster binding 4 iron, 4 sulfur cluster binding metal cluster binding cation binding metal ion binding pyrimidine nucleobase binding nucleobase binding uracil binding	pyrimidine-containing compound metabolic process catabolic process thymine catabolic process pyrimidine-containing compound catabolic process primary metabolic process pyrimidine nucleobase catabolic process nucleobase-containing compound metabolic process pyrimidine nucleobase metabolic process thymine metabolic process nucleobase-containing small molecule metabolic process nucleobase catabolic process nucleobase metabolic process small molecule metabolic process metabolic process pyrimidine-containing compound metabolic process catabolic process thymine catabolic process pyrimidine-containing compound catabolic process primary metabolic process pyrimidine nucleobase catabolic process nucleobase-containing compound metabolic process pyrimidine nucleobase metabolic process thymine metabolic process nucleobase-containing small molecule metabolic process nucleobase catabolic process nucleobase metabolic process small molecule metabolic process metabolic process beta-alanine metabolic process oxoacid metabolic process small molecule biosynthetic process cellular biosynthetic process cellular metabolic process carboxylic acid metabolic process amino acid metabolic process organic acid metabolic process organic acid biosynthetic process beta-alanine biosynthetic process carboxylic acid biosynthetic process non-proteinogenic amino acid metabolic process amino acid biosynthetic process biosynthetic process cellular process non-proteinogenic amino acid biosynthetic process glycosyl compound metabolic process deoxyribonucleoside metabolic process thymidine catabolic process carbohydrate derivative metabolic process pyrimidine nucleoside metabolic process carbohydrate derivative catabolic process pyrimidine nucleoside catabolic process glycosyl compound catabolic process nucleoside metabolic process pyrimidine deoxyribonucleoside catabolic process nucleobase-containing compound catabolic process nucleobase-containing small molecule catabolic process nucleoside catabolic process deoxyribonucleoside catabolic process small molecule catabolic process pyrimidine deoxyribonucleoside metabolic process thymidine metabolic process uracil metabolic process uracil catabolic process	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR013785	Aldolase-type TIM barrel	Homologous Superfamily
A, B, C, D	IPR005720	Dihydroorotate dehydrogenase, catalytic	Domain
A, B, C, D	IPR036188	FAD/NAD(P)-binding domain superfamily	Homologous Superfamily
A, B, C, D	IPR009051	Alpha-helical ferredoxin	Homologous Superfamily
A, B, C, D	IPR017900	4Fe-4S ferredoxin, iron-sulphur binding, conserved site	Conserved Site
A, B, C, D	IPR028261	Dihydroprymidine dehydrogenase domain II	Domain
A, B, C, D	IPR017896	4Fe-4S ferredoxin-type, iron-sulphur binding domain	Domain
A, B, C, D	IPR023753	FAD/NAD(P)-binding domain	Domain

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

Chains	Enzyme Name	Description	Catalytic Residues
C	dihydropyrimidine dehydrogenase (NADP+) M-CSA #800	Mammalian dihydropyrimidine dehydrogenase catalyses the reduction of uracil or thymine to dihydrouracil or dihydrothymine respectively. This reaction represents an important step in the pathway of pyrimidine degradation in cells, but is particularly important to medicine because the anticancer drug 5-flourouracil, though shown to be effective, is also a substrate for this enzyme, thus its effectiveness is reduced. The development of specific inhibitors is therefore paramount in order to reduce the cost and side effects of treatment with this drug.	Defined by 3 residues: LYS:C-574ALA:C-671LYS:C-709 \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 1.3.1.2 (PDB Primary Data) Search M-CSA Motif + EC 1.3.1.2