2R3V

The Biochemical and Structural Basis for Feedback Inhibition of Mevalonate Kinase and Isoprenoid Metabolism

External Resource: Annotation

Domain Annotation: SCOP/SCOPe 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	d2r3va1	Alpha and beta proteins (a+b)	Ribosomal protein S5 domain 2-like	Ribosomal protein S5 domain 2-like	GHMP Kinase, N-terminal domain	Mevalonate kinase	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d2r3va2	Alpha and beta proteins (a+b)	Ferredoxin-like	GHMP Kinase, C-terminal domain	Mevalonate kinase	Mevalonate kinase	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d2r3vb1	Alpha and beta proteins (a+b)	Ribosomal protein S5 domain 2-like	Ribosomal protein S5 domain 2-like	GHMP Kinase, N-terminal domain	Mevalonate kinase	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d2r3vb2	Alpha and beta proteins (a+b)	Ferredoxin-like	GHMP Kinase, C-terminal domain	Mevalonate kinase	Mevalonate kinase	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d2r3vc1	Alpha and beta proteins (a+b)	Ribosomal protein S5 domain 2-like	Ribosomal protein S5 domain 2-like	GHMP Kinase, N-terminal domain	Mevalonate kinase	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d2r3vc2	Alpha and beta proteins (a+b)	Ferredoxin-like	GHMP Kinase, C-terminal domain	Mevalonate kinase	Mevalonate kinase	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d2r3vd1	Alpha and beta proteins (a+b)	Ribosomal protein S5 domain 2-like	Ribosomal protein S5 domain 2-like	GHMP Kinase, N-terminal domain	Mevalonate kinase	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d2r3vd2	Alpha and beta proteins (a+b)	Ferredoxin-like	GHMP Kinase, C-terminal domain	Mevalonate kinase	Mevalonate kinase	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	GHMP_kinases_N	e2r3vA5	A: a+b two layers	X: Ribosomal protein S5 domain 2-like (From Topology)	H: Ribosomal protein S5 domain 2-like (From Topology)	T: Ribosomal protein S5 domain 2-like	F: GHMP_kinases_N	ECOD (1.6)
A	GHMP_kinases_C	e2r3vA6	A: a+b two layers	X: Alpha-beta plaits	H: GHMP Kinase, C-terminal domain (From Topology)	T: GHMP Kinase, C-terminal domain	F: GHMP_kinases_C	ECOD (1.6)
B	GHMP_kinases_N	e2r3vB1	A: a+b two layers	X: Ribosomal protein S5 domain 2-like (From Topology)	H: Ribosomal protein S5 domain 2-like (From Topology)	T: Ribosomal protein S5 domain 2-like	F: GHMP_kinases_N	ECOD (1.6)
B	GHMP_kinases_C	e2r3vB2	A: a+b two layers	X: Alpha-beta plaits	H: GHMP Kinase, C-terminal domain (From Topology)	T: GHMP Kinase, C-terminal domain	F: GHMP_kinases_C	ECOD (1.6)
C	GHMP_kinases_N	e2r3vC2	A: a+b two layers	X: Ribosomal protein S5 domain 2-like (From Topology)	H: Ribosomal protein S5 domain 2-like (From Topology)	T: Ribosomal protein S5 domain 2-like	F: GHMP_kinases_N	ECOD (1.6)
C	GHMP_kinases_C	e2r3vC1	A: a+b two layers	X: Alpha-beta plaits	H: GHMP Kinase, C-terminal domain (From Topology)	T: GHMP Kinase, C-terminal domain	F: GHMP_kinases_C	ECOD (1.6)
D	GHMP_kinases_N	e2r3vD2	A: a+b two layers	X: Ribosomal protein S5 domain 2-like (From Topology)	H: Ribosomal protein S5 domain 2-like (From Topology)	T: Ribosomal protein S5 domain 2-like	F: GHMP_kinases_N	ECOD (1.6)
D	GHMP_kinases_C	e2r3vD1	A: a+b two layers	X: Alpha-beta plaits	H: GHMP Kinase, C-terminal domain (From Topology)	T: GHMP Kinase, C-terminal domain	F: GHMP_kinases_C	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.230.10	Alpha Beta	2-Layer Sandwich	Ribosomal Protein S5	domain 2	CATH (4.3.0)
A	3.30.70.890	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	GHMP kinase, C-terminal domain	CATH (4.3.0)
B	3.30.230.10	Alpha Beta	2-Layer Sandwich	Ribosomal Protein S5	domain 2	CATH (4.3.0)
B	3.30.70.890	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	GHMP kinase, C-terminal domain	CATH (4.3.0)
C	3.30.230.10	Alpha Beta	2-Layer Sandwich	Ribosomal Protein S5	domain 2	CATH (4.3.0)
C	3.30.70.890	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	GHMP kinase, C-terminal domain	CATH (4.3.0)
D	3.30.230.10	Alpha Beta	2-Layer Sandwich	Ribosomal Protein S5	domain 2	CATH (4.3.0)
D	3.30.70.890	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	GHMP kinase, C-terminal domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF08544	GHMP kinases C terminal (GHMP_kinases_C)	GHMP kinases C terminal	-	Family
A, B, C, D	PF00288	GHMP kinases N terminal domain (GHMP_kinases_N)	GHMP kinases N terminal domain	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	Mevalonate kinase	cation binding magnesium ion binding ion binding binding metal ion binding small molecule binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding purine nucleotide binding organic cyclic compound binding anion binding cation binding magnesium ion binding ion binding binding metal ion binding small molecule binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding mevalonate kinase activity kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups identical protein binding protein binding	regulation of defense response regulation of biological process response to stimulus regulation of response to external stimulus negative regulation of inflammatory response defense response negative regulation of response to stimulus biological regulation negative regulation of biological process response to external stimulus regulation of inflammatory response regulation of response to stimulus response to stress negative regulation of response to external stimulus regulation of response to stress regulation of defense response regulation of biological process response to stimulus regulation of response to external stimulus negative regulation of inflammatory response defense response negative regulation of response to stimulus biological regulation negative regulation of biological process response to external stimulus regulation of inflammatory response regulation of response to stimulus response to stress negative regulation of response to external stimulus regulation of response to stress negative regulation of defense response inflammatory response isoprenoid biosynthetic process cellular biosynthetic process cellular metabolic process lipid biosynthetic process primary metabolic process biosynthetic process cellular lipid metabolic process metabolic process cellular process lipid metabolic process isoprenoid metabolic process isopentenyl diphosphate biosynthetic process acetyl-CoA metabolic process phospholipid metabolic process nucleobase-containing compound metabolic process acyl-CoA metabolic process nucleobase-containing small molecule metabolic 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 phospholipid biosynthetic process purine-containing compound metabolic process organophosphate metabolic process organophosphate biosynthetic process isopentenyl diphosphate biosynthetic process, mevalonate pathway isopentenyl diphosphate metabolic process secondary alcohol biosynthetic process small molecule biosynthetic process cholesterol biosynthetic process organic hydroxy compound metabolic process sterol metabolic process steroid metabolic process cholesterol metabolic process alcohol metabolic process secondary alcohol metabolic process sterol biosynthetic process organic hydroxy compound biosynthetic process alcohol biosynthetic process steroid biosynthetic process	membrane-bounded organelle intracellular organelle intracellular anatomical structure organelle peroxisome microbody cytoplasm cellular anatomical entity intracellular membrane-bounded organelle cytosol

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR006205	Mevalonate kinase	Family
A, B, C, D	IPR013750	GHMP kinase, C-terminal domain	Domain
A, B, C, D	IPR036554	GHMP kinase, C-terminal domain superfamily	Homologous Superfamily
A, B, C, D	IPR006204	GHMP kinase N-terminal domain	Domain
A, B, C, D	IPR006203	GHMP kinase, ATP-binding, conserved site	Conserved Site
A, B, C, D	IPR020568	Ribosomal protein uS5 domain 2-type superfamily	Homologous Superfamily
A, B, C, D	IPR014721	Small ribosomal subunit protein uS5 domain 2-type fold, subgroup	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: Q03426	mevalonic aciduria porokeratosis 3, disseminated superficial actinic type hyperimmunoglobulinemia D with periodic fever Arthralgia porokeratosis of Mibelli exanthem osteosarcoma porokeratosis cataract heart disease inborn errors of metabolism malignant mesothelioma periodic fever syndrome cholestasis disseminated superficial actinic porokeratosis mevalonic aciduria porokeratosis 3, disseminated superficial actinic type hyperimmunoglobulinemia D with periodic fever Arthralgia porokeratosis of Mibelli exanthem osteosarcoma porokeratosis cataract heart disease inborn errors of metabolism malignant mesothelioma periodic fever syndrome cholestasis disseminated superficial actinic porokeratosis familial Mediterranean fever hepatocellular carcinoma intellectual disability psoriasis autosomal dominant familial periodic fever

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.