2V0M

Crystal structure of human P450 3A4 in complex with ketoconazole

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)
A	d2v0ma1	All alpha proteins	Cytochrome P450	Cytochrome P450	Cytochrome P450	Mammalian cytochrome P450 3a4	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d2v0mb1	All alpha proteins	Cytochrome P450	Cytochrome P450	Cytochrome P450	Mammalian cytochrome P450 3a4	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d2v0mc1	All alpha proteins	Cytochrome P450	Cytochrome P450	Cytochrome P450	Mammalian cytochrome P450 3a4	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d2v0md1	All alpha proteins	Cytochrome P450	Cytochrome P450	Cytochrome P450	Mammalian cytochrome P450 3a4	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	Cytochrome P450	8040388	3001061	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Cytochrome P450	8040388	3001061	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Cytochrome P450	8040388	3001061	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Cytochrome P450	8040388	3001061	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	p450	e2v0mA1	A: alpha arrays	X: Cytochrome P450 (From Topology)	H: Cytochrome P450 (From Topology)	T: Cytochrome P450	F: p450	ECOD (1.6)
B	p450	e2v0mB1	A: alpha arrays	X: Cytochrome P450 (From Topology)	H: Cytochrome P450 (From Topology)	T: Cytochrome P450	F: p450	ECOD (1.6)
C	p450	e2v0mC1	A: alpha arrays	X: Cytochrome P450 (From Topology)	H: Cytochrome P450 (From Topology)	T: Cytochrome P450	F: p450	ECOD (1.6)
D	p450	e2v0mD1	A: alpha arrays	X: Cytochrome P450 (From Topology)	H: Cytochrome P450 (From Topology)	T: Cytochrome P450	F: p450	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.10.630.10	Mainly Alpha	Orthogonal Bundle	Cytochrome p450	Cytochrome P450	CATH (4.3.0)
B	1.10.630.10	Mainly Alpha	Orthogonal Bundle	Cytochrome p450	Cytochrome P450	CATH (4.3.0)
C	1.10.630.10	Mainly Alpha	Orthogonal Bundle	Cytochrome p450	Cytochrome P450	CATH (4.3.0)
D	1.10.630.10	Mainly Alpha	Orthogonal Bundle	Cytochrome p450	Cytochrome P450	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF00067	Cytochrome P450 (p450)	Cytochrome P450	Cytochrome P450s are haem-thiolate proteins [6] involved in the oxidative degradation of various compounds. They are particularly well known for their role in the degradation of environmental toxins and mutagens. They can be divided into 4 classes, a ...	Cytochrome P450s are haem-thiolate proteins [6] involved in the oxidative degradation of various compounds. They are particularly well known for their role in the degradation of environmental toxins and mutagens. They can be divided into 4 classes, according to the method by which electrons from NAD(P)H are delivered to the catalytic site. Sequence conservation is relatively low within the family - there are only 3 absolutely conserved residues - but their general topography and structural fold are highly conserved. The conserved core is composed of a coil termed the 'meander', a four-helix bundle, helices J and K, and two sets of beta-sheets. These constitute the haem-binding loop (with an absolutely conserved cysteine that serves as the 5th ligand for the haem iron), the proton-transfer groove and the absolutely conserved EXXR motif in helix K. While prokaryotic P450s are soluble proteins, most eukaryotic P450s are associated with microsomal membranes. their general enzymatic function is to catalyse regiospecific and stereospecific oxidation of non-activated hydrocarbons at physiological temperatures [6].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	CYTOCHROME P450 3A4	vitamin D 24-hydroxylase activity monooxygenase activity oxidoreductase activity catalytic activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen aromatase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen vitamin D3 25-hydroxylase activity vitamin D 25-hydroxylase activity retinoic acid 4-hydroxylase activity oxidoreductase activity, acting on CH or CH2 groups, quinone or similar compound as acceptor caffeine oxidase activity oxidoreductase activity, acting on CH or CH2 groups testosterone 6-beta-hydroxylase activity vitamin D 24-hydroxylase activity monooxygenase activity oxidoreductase activity catalytic activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen aromatase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen vitamin D3 25-hydroxylase activity vitamin D 25-hydroxylase activity retinoic acid 4-hydroxylase activity oxidoreductase activity, acting on CH or CH2 groups, quinone or similar compound as acceptor caffeine oxidase activity oxidoreductase activity, acting on CH or CH2 groups testosterone 6-beta-hydroxylase activity steroid hydroxylase activity cation binding transition metal ion binding iron ion binding ion binding binding metal ion binding small molecule binding anandamide 8,9 epoxidase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen anandamide epoxidase activity estrogen 16-alpha-hydroxylase activity 1,8-cineole 2-exo-monooxygenase activity vitamin D 23-hydroxylase activity 1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity quinine 3-monooxygenase activity anandamide 11,12 epoxidase activity oxygen binding estrogen 2-hydroxylase activity anandamide 14,15 epoxidase activity organic cyclic compound binding tetrapyrrole binding heme binding steroid binding lipid binding protein binding enzyme binding	cellular metabolic process cellular lipid metabolic process lipid modification primary metabolic process metabolic process cellular process lipid hydroxylation lipid metabolic process regulation of hormone levels steroid metabolic process biological regulation androgen metabolic process regulation of biological quality hormone metabolic process cellular metabolic process cellular lipid metabolic process lipid modification primary metabolic process metabolic process cellular process lipid hydroxylation lipid metabolic process regulation of hormone levels steroid metabolic process biological regulation androgen metabolic process regulation of biological quality hormone metabolic process aflatoxin metabolic process mycotoxin metabolic process organic heteropentacyclic compound metabolic process toxin metabolic process secondary metabolic process catabolic process alkaloid catabolic process alkaloid metabolic process lipid catabolic process fat-soluble vitamin metabolic process organic hydroxy compound metabolic process vitamin D catabolic process vitamin D metabolic process fat-soluble vitamin catabolic process vitamin catabolic process vitamin metabolic process cellular catabolic process steroid catabolic process organic hydroxy compound catabolic process small molecule metabolic process small molecule catabolic process cellular response to stimulus response to stimulus cellular response to xenobiotic stimulus xenobiotic catabolic process xenobiotic metabolic process response to xenobiotic stimulus cellular response to chemical stimulus response to chemical diterpenoid metabolic process alcohol metabolic process retinoid metabolic process olefinic compound metabolic process retinol metabolic process terpenoid metabolic process isoprenoid metabolic process primary alcohol metabolic process oxidative demethylation demethylation oxoacid metabolic process carboxylic acid metabolic process organic acid metabolic process retinoic acid metabolic process monocarboxylic acid metabolic process estrogen metabolic process secondary alcohol metabolic process sterol metabolic process cholesterol metabolic process fatty acid metabolic process long-chain fatty acid metabolic process monocarboxylic acid biosynthetic process small molecule biosynthetic process cellular biosynthetic process long-chain fatty acid biosynthetic process lipid biosynthetic process organic acid biosynthetic process fatty acid biosynthetic process carboxylic acid biosynthetic process biosynthetic process monoterpenoid metabolic process	intracellular anatomical structure cytoplasm cellular anatomical entity membrane-bounded organelle intracellular organelle organelle intracellular membrane-bounded organelle organelle subcompartment membrane endomembrane system endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum organelle membrane intracellular anatomical structure cytoplasm cellular anatomical entity membrane-bounded organelle intracellular organelle organelle intracellular membrane-bounded organelle organelle subcompartment membrane endomembrane system endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum organelle membrane endoplasmic reticulum membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR008072	Cytochrome P450, E-class, CYP3A	Family
A, B, C, D	IPR017972	Cytochrome P450, conserved site	Conserved Site
A, B, C, D	IPR050705	Cytochrome P450 3A	Family
A, B, C, D	IPR001128	Cytochrome P450	Family
A, B, C, D	IPR036396	Cytochrome P450 superfamily	Homologous Superfamily
A, B, C, D	IPR002402	Cytochrome P450, E-class, group II	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: P08684	osteosarcoma hepatitis C virus infection torsades de pointes breast carcinoma prostate cancer malignant ependymoma Mammary Neoplasms, Human pancreatic ductal adenocarcinoma adrenal cortex adenoma large cell medulloblastoma oligodendroglioma pancreatic intraductal papillary-mucinous neoplasm psoriasis astrocytic tumor cancer osteosarcoma hepatitis C virus infection torsades de pointes breast carcinoma prostate cancer malignant ependymoma Mammary Neoplasms, Human pancreatic ductal adenocarcinoma adrenal cortex adenoma large cell medulloblastoma oligodendroglioma pancreatic intraductal papillary-mucinous neoplasm psoriasis astrocytic tumor cancer diarrheal disease drug-induced liver injury liver disease schizophrenia breast cancer cutaneous lupus erythematosus HIV infectious disease

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.