1DQA

COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH HMG, COA, AND NADP+

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
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)
B	d1dqab1	Alpha and beta proteins (a+b)	Ferredoxin-like	NAD-binding domain of HMG-CoA reductase	NAD-binding domain of HMG-CoA reductase	NAD-binding domain of HMG-CoA reductase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d1dqab4	Alpha and beta proteins (a+b)	Substrate-binding domain of HMG-CoA reductase	Substrate-binding domain of HMG-CoA reductase	Substrate-binding domain of HMG-CoA reductase	Substrate-binding domain of HMG-CoA reductase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d1dqac1	Alpha and beta proteins (a+b)	Ferredoxin-like	NAD-binding domain of HMG-CoA reductase	NAD-binding domain of HMG-CoA reductase	NAD-binding domain of HMG-CoA reductase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d1dqac4	Alpha and beta proteins (a+b)	Substrate-binding domain of HMG-CoA reductase	Substrate-binding domain of HMG-CoA reductase	Substrate-binding domain of HMG-CoA reductase	Substrate-binding domain of HMG-CoA reductase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1dqaa1	Alpha and beta proteins (a+b)	Ferredoxin-like	NAD-binding domain of HMG-CoA reductase	NAD-binding domain of HMG-CoA reductase	NAD-binding domain of HMG-CoA reductase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1dqaa4	Alpha and beta proteins (a+b)	Substrate-binding domain of HMG-CoA reductase	Substrate-binding domain of HMG-CoA reductase	Substrate-binding domain of HMG-CoA reductase	Substrate-binding domain of HMG-CoA reductase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d1dqad1	Alpha and beta proteins (a+b)	Ferredoxin-like	NAD-binding domain of HMG-CoA reductase	NAD-binding domain of HMG-CoA reductase	NAD-binding domain of HMG-CoA reductase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d1dqad4	Alpha and beta proteins (a+b)	Substrate-binding domain of HMG-CoA reductase	Substrate-binding domain of HMG-CoA reductase	Substrate-binding domain of HMG-CoA reductase	Substrate-binding domain of HMG-CoA reductase	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)
B	SCOP2B Superfamily	NAD-binding domain of HMG-CoA reductase	8035520	3001200	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Substrate-binding domain of HMG-CoA reductase	8037275	3001471	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Substrate-binding domain of HMG-CoA reductase	8037275	3001471	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	NAD-binding domain of HMG-CoA reductase	8035520	3001200	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Substrate-binding domain of HMG-CoA reductase	8037275	3001471	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Substrate-binding domain of HMG-CoA reductase	8037275	3001471	SCOP2B (2022-06-29)
A	SCOP2 Family	NAD-binding domain of HMG-CoA reductase	8023140	4001276	SCOP2 (2022-06-29)
A	SCOP2 Family	Substrate-binding domain of HMG-CoA reductase	8024896	4002601	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	NAD-binding domain of HMG-CoA reductase	8035520	3001200	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Substrate-binding domain of HMG-CoA reductase	8037275	3001471	SCOP2 (2022-06-29)
D	SCOP2B Superfamily	Substrate-binding domain of HMG-CoA reductase	8037275	3001471	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Substrate-binding domain of HMG-CoA reductase	8037275	3001471	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	NAD-binding domain of HMG-CoA reductase	8035520	3001200	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)
B	HMG-CoA_red_2nd	e1dqaB1	A: a+b two layers	X: Alpha-beta plaits	H: HMG-CoA reductase	T: NAD-binding domain of HMG-CoA reductase	F: HMG-CoA_red_2nd	ECOD (1.6)
B	HMG-CoA_red_1st	e1dqaB2	A: a+b two layers	X: Alpha-beta plaits	H: HMG-CoA reductase	T: Substrate-binding domain of HMG-CoA reductase	F: HMG-CoA_red_1st	ECOD (1.6)
C	HMG-CoA_red_2nd	e1dqaC1	A: a+b two layers	X: Alpha-beta plaits	H: HMG-CoA reductase	T: NAD-binding domain of HMG-CoA reductase	F: HMG-CoA_red_2nd	ECOD (1.6)
C	HMG-CoA_red_1st	e1dqaC2	A: a+b two layers	X: Alpha-beta plaits	H: HMG-CoA reductase	T: Substrate-binding domain of HMG-CoA reductase	F: HMG-CoA_red_1st	ECOD (1.6)
A	HMG-CoA_red_2nd	e1dqaA1	A: a+b two layers	X: Alpha-beta plaits	H: HMG-CoA reductase	T: NAD-binding domain of HMG-CoA reductase	F: HMG-CoA_red_2nd	ECOD (1.6)
A	HMG-CoA_red_1st	e1dqaA2	A: a+b two layers	X: Alpha-beta plaits	H: HMG-CoA reductase	T: Substrate-binding domain of HMG-CoA reductase	F: HMG-CoA_red_1st	ECOD (1.6)
D	HMG-CoA_red_2nd	e1dqaD1	A: a+b two layers	X: Alpha-beta plaits	H: HMG-CoA reductase	T: NAD-binding domain of HMG-CoA reductase	F: HMG-CoA_red_2nd	ECOD (1.6)
D	HMG-CoA_red_1st	e1dqaD2	A: a+b two layers	X: Alpha-beta plaits	H: HMG-CoA reductase	T: Substrate-binding domain of HMG-CoA reductase	F: HMG-CoA_red_1st	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	1.10.3270.10	Mainly Alpha	Orthogonal Bundle	HMGR, N-terminal domain	HMGR, N-terminal domain	CATH (4.3.0)
B	3.90.770.10	Alpha Beta	Alpha-Beta Complex	3-hydroxy-3-methylglutaryl-coenzyme A Reductase	Chain A, domain 2	CATH (4.3.0)
B	3.30.70.420	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	Hydroxymethylglutaryl-CoA reductase, class I/II, NAD/NADP-binding domain	CATH (4.3.0)
C	1.10.3270.10	Mainly Alpha	Orthogonal Bundle	HMGR, N-terminal domain	HMGR, N-terminal domain	CATH (4.3.0)
C	3.90.770.10	Alpha Beta	Alpha-Beta Complex	3-hydroxy-3-methylglutaryl-coenzyme A Reductase	Chain A, domain 2	CATH (4.3.0)
C	3.30.70.420	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	Hydroxymethylglutaryl-CoA reductase, class I/II, NAD/NADP-binding domain	CATH (4.3.0)
A	1.10.3270.10	Mainly Alpha	Orthogonal Bundle	HMGR, N-terminal domain	HMGR, N-terminal domain	CATH (4.3.0)
A	3.90.770.10	Alpha Beta	Alpha-Beta Complex	3-hydroxy-3-methylglutaryl-coenzyme A Reductase	Chain A, domain 2	CATH (4.3.0)
A	3.30.70.420	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	Hydroxymethylglutaryl-CoA reductase, class I/II, NAD/NADP-binding domain	CATH (4.3.0)
D	1.10.3270.10	Mainly Alpha	Orthogonal Bundle	HMGR, N-terminal domain	HMGR, N-terminal domain	CATH (4.3.0)
D	3.90.770.10	Alpha Beta	Alpha-Beta Complex	3-hydroxy-3-methylglutaryl-coenzyme A Reductase	Chain A, domain 2	CATH (4.3.0)
D	3.30.70.420	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	Hydroxymethylglutaryl-CoA reductase, class I/II, NAD/NADP-binding domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF00368	Hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA_red)	Hydroxymethylglutaryl-coenzyme A reductase	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	PROTEIN (HMG-COA REDUCTASE)	binding nucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding heterocyclic compound binding NADPH binding NADP binding small molecule binding GTPase regulator activity enzyme regulator activity binding nucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding heterocyclic compound binding NADPH binding NADP binding small molecule binding GTPase regulator activity enzyme regulator activity nucleoside-triphosphatase regulator activity molecular function regulator activity coenzyme A binding amide binding sulfur compound binding oxidoreductase activity oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor oxidoreductase activity, acting on CH-OH group of donors hydroxymethylglutaryl-CoA reductase (NADPH) activity catalytic activity	negative regulation of protein transport protein localization regulation of localization establishment of protein localization cellular localization nitrogen compound transport regulation of cellular process regulation of protein localization transport negative regulation of biological process negative regulation of transport protein localization to extracellular region localization negative regulation of secretion regulation of secretion by cell negative regulation of protein transport protein localization regulation of localization establishment of protein localization cellular localization nitrogen compound transport regulation of cellular process regulation of protein localization transport negative regulation of biological process negative regulation of transport protein localization to extracellular region localization negative regulation of secretion regulation of secretion by cell secretion by cell cellular macromolecule localization negative regulation of cellular process negative regulation of secretion by cell negative regulation of protein localization regulation of biological process regulation of transport secretion biological regulation regulation of establishment of protein localization establishment of protein localization to extracellular region negative regulation of establishment of protein localization export from cell regulation of protein transport protein secretion establishment of localization regulation of secretion regulation of protein secretion negative regulation of protein secretion protein transport regulation of cellular localization macromolecule localization cellular process biosynthetic process isoprenoid biosynthetic process lipid biosynthetic process primary metabolic process metabolic process lipid metabolic process isoprenoid metabolic process response to light stimulus multicellular organismal process system process learning learning or memory nervous system process response to stimulus visual learning visual behavior cognition associative learning behavior response to radiation response to abiotic stimulus 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 small molecule metabolic process steroid biosynthetic process cellular response to stimulus regulation of signaling signaling regulation of signal transduction regulation of MAPK cascade intracellular signal transduction cell communication regulation of intracellular signal transduction regulation of response to stimulus intracellular signaling cassette MAPK cascade regulation of cell communication ERK1 and ERK2 cascade signal transduction regulation of ERK1 and ERK2 cascade nucleoside phosphate metabolic process purine-containing compound metabolic process nucleobase-containing compound metabolic process organophosphate metabolic process nucleobase-containing small molecule metabolic process phosphate-containing compound metabolic process sulfur compound metabolic process amide metabolic process phosphorus metabolic process coenzyme A metabolic process catabolic process macromolecule catabolic process negative regulation of protein catabolic process regulation of primary metabolic process protein metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process negative regulation of catabolic process regulation of protein metabolic process negative regulation of metabolic process protein catabolic process regulation of macromolecule metabolic process regulation of catabolic process macromolecule metabolic process regulation of metabolic process regulation of protein catabolic process negative regulation of amyloid-beta clearance regulation of multicellular organismal process amyloid-beta clearance regulation of amyloid-beta clearance negative regulation of multicellular organismal process positive regulation of cell communication modulation of chemical synaptic transmission positive regulation of biological process long-term synaptic potentiation synaptic signaling regulation of biological quality positive regulation of cellular process regulation of synaptic plasticity trans-synaptic signaling cell-cell signaling positive regulation of synaptic transmission chemical synaptic transmission regulation of trans-synaptic signaling anterograde trans-synaptic signaling positive regulation of signaling	membrane-bounded organelle intracellular anatomical structure organelle subcompartment membrane intracellular membrane-bounded organelle endomembrane system endoplasmic reticulum subcompartment intracellular organelle cellular anatomical structure organelle nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum cytoplasm organelle membrane membrane-bounded organelle intracellular anatomical structure organelle subcompartment membrane intracellular membrane-bounded organelle endomembrane system endoplasmic reticulum subcompartment intracellular organelle cellular anatomical structure organelle nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum cytoplasm organelle membrane endoplasmic reticulum membrane peroxisome microbody membrane bounding membrane of organelle peroxisomal membrane microbody

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR004816	Hydroxymethylglutaryl-CoA reductase, metazoan	Family
A, B, C, D	IPR000731	Sterol-sensing domain	Domain
A, B, C, D	IPR053958	HMGCR/SNAP/NPC1-like, sterol-sensing domain	Domain
A, B, C, D	IPR002202	Hydroxymethylglutaryl-CoA reductase, class I/II	Family
A, B, C, D	IPR009023	Hydroxymethylglutaryl-CoA reductase, class I/II, NAD/NADP-binding domain superfamily	Homologous Superfamily
A, B, C, D	IPR004554	Hydroxymethylglutaryl-CoA reductase, eukaryotic/archaeal type	Family
A, B, C, D	IPR023282	Hydroxymethylglutaryl-CoA reductase, N-terminal	Homologous Superfamily
A, B, C, D	IPR009029	Hydroxymethylglutaryl-CoA reductase, class I/II, substrate-binding domain superfamily	Homologous Superfamily
A, B, C, D	IPR023074	Hydroxymethylglutaryl-CoA reductase, class I/II, catalytic domain superfamily	Homologous Superfamily
A, B, C, D	IPR023076	Hydroxymethylglutaryl-CoA reductase, class I/II, conserved site	Conserved Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: P04035	Hypercholesterolemia myopathy chronic kidney disease autoimmune disease hepatocellular carcinoma Q fever hypoalphalipoproteinemia malignant pancreatic neoplasm atherosclerosis osteosarcoma pancreatic intraductal papillary-mucinous carcinoma Pick disease Prinzmetal angina familial hyperlipidemia sinusitis Hypercholesterolemia myopathy chronic kidney disease autoimmune disease hepatocellular carcinoma Q fever hypoalphalipoproteinemia malignant pancreatic neoplasm atherosclerosis osteosarcoma pancreatic intraductal papillary-mucinous carcinoma Pick disease Prinzmetal angina familial hyperlipidemia sinusitis gastric carcinoma ulcerative colitis hyperlipoproteinemia type 3 inherited lipid metabolism disorder muscle tissue disease ovarian cancer pancreatic intraductal papillary-mucinous neoplasm ductal breast carcinoma in situ psoriasis gallstones hypertriglyceridemia interstitial lung disease malignant mesothelioma muscular disease arteriosclerosis disorder pancreatic ductal adenocarcinoma coronary artery disease pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia exocrine pancreatic carcinoma gastric cancer tuberculosis

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

Chains	Enzyme Name	Description	Catalytic Residues
A, B	hydroxymethylglutaryl-CoA reductase (NADPH) M-CSA #93	Hydroxymethylglutaryl-CoA reductase catalyses the committed step in the biosynthesis of isoprenoids, compounds involved in diverse cellular functions such as sterol synthesis and growth control. The precursor of such products is melvalonic acid and concentrations of mevalonate are tightly controlled within cells. This is achieved through the activity of 3-hydroxy-3-methylglutaryl-CoA reductase which catalyses the four electron reduction reduction of 3-hydroxy-3-methylglutaryl-CoA to mevalonate. The activity of 3-hydroxy-3-methylglutaryl-CoA reductase is controlled physiologically through synthesis, degradation and phosphorylation as well as clinically, being the target of several high cholesterol drugs.	Defined by 4 residues: LYS:A-270 [auth A-691]ASP:A-346 [auth A-767]GLU:B-138 [auth B-559]HIS:B-445 [auth B-866] \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 1.1.1.34 (PDB Primary Data) Search M-CSA Motif + EC 1.1.1.34

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.