hydroxymethylglutaryl-CoA reductase (NADPH)
hydroxymethylglutaryl coenzyme A reductase (reduced nicotinamideadenine dinucleotide phosphate)
3-hydroxy-3-methylglutaryl-CoA reductase
beta-hydroxy-beta-methylglutaryl coenzyme A reductase
hydroxymethylglutaryl CoA reductase (NADPH)
S-3-hydroxy-3-methylglutaryl-CoA reductase
NADPH-hydroxymethylglutaryl-CoA reductase
HMGCoA reductase-mevalonate:NADP-oxidoreductase (acetylating-CoA)
3-hydroxy-3-methylglutaryl CoA reductase (NADPH)
hydroxymethylglutaryl-CoA reductase (NADPH2)
This enzyme is composed of the N-terminal transmembrane domain, linker region, and the C-terminal catalytic domains. Tertiary structures have been solved for the C-terminal catalytic domains (see [7]). HMG-CoA reductase from Pseudomonas mevalonii, which does not have transmembrane domain, is homologous to this enzyme (EC 1.1.1.88; D00607 in EzCatDB). The active site of this enzyme is similar to that of the counterpart enzyme, but slightly different. Therefor the catalytic reaction is also similar but slightly different from that of the homologous enzyme. According to the literature [13], [19] and [20], this enzyme catalyzes the following reactions: (A) Hydride transfer from NADPH to HMG-CoA, forming the first intermediate, Mevaldyl-CoA (I00101): (A0) Asp767 may modulate the charge/activity of Glu559 and Lys691. (Asp767 raise the pKa of Glu559 so that it could be protonated.) (A1) Hydride transfer occurs from nicotinamide group of NADPH to the carbonyl carbon of the substrate HMG-CoA. Simultaneously, Lys691 and the protonated Glu559 stabilizes the negative charge on the oxygen during the formation of Mevaldyl-CoA. (B) Eliminative double-bond formation; Elimination of CoASH from Mevaldyl-CoA, forming the second intermediate, Mevaldehyde (I00102): (B0) Asp767 may modulate the charge/activity of Glu559 and Lys691. (B1) Glu559 and Lys691 stabilizes the negative charge on the oxygen atom of the intermediate. (B2) His866 on the C-terminal movable domain acts as general acid to protonate the sulfur atom (or thioanion) of the eliminated group, CoA, to complete the reaction. This elimination reaction seems to be E1cB-like reaction. (C) Hydride transfer from NADPH to Mevaldehyde, forming product, Mevalonate: (C0) Asp767 may modulate the charge/activity of Glu559 and Lys691. (C1) Lys691 acts as a general acid to protonate the carbonyl oxygen of Mevaldehyde. At the same time, hydride transfer occurs from nicotinamide group of NADH to the carbonyl carbon of Mevaldehyde.
3-hydroxy-3-methylglutaryl-coenzyme A Reductase; Chain A, domain 2
Regulation of vertebrate liver HMG-CoA reductase via reversible modulation of its catalytic activity.
Syrian hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase expressed in Escherichia coli: production of homogeneous protein.
Biochemical characterization of two forms of 3-hydroxy-3-methylglutaryl-CoA reductase kinase from cauliflower (Brassica oleracia).
The active site of hamster 3-hydroxy-3-methylglutaryl-CoA reductase resides at the subunit interface and incorporates catalytically essential acidic residues from separate polypeptides.
Catalysis by Syrian hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Proposed roles of histidine 865, glutamate 558, and aspartate 766.
Modulation of Syrian hamster 3-hydroxy-3-methylglutaryl-CoA reductase activity by phosphorylation. Role of serine 871.
Phosphorylation of Ser871 impairs the function of His865 of Syrian hamster 3-hydroxy-3-methylglutaryl-CoA reductase.
Arabidopsis thaliana contains two differentially expressed 3-hydroxy-3-methylglutaryl-CoA reductase genes, which encode microsomal forms of the enzyme.
Aminoethylcysteine can replace the function of the essential active site lysine of Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl coenzyme A reductase.
Purification, characterization, and cloning of a eubacterial 3-hydroxy-3-methylglutaryl coenzyme A reductase, a key enzyme involved in biosynthesis of terpenoids.
The structure of the catalytic portion of human HMG-CoA reductase.
Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation.
Cloning and characterization of the gene encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase in melon (Cucumis melo L. reticulatus).
Structural mechanism for statin inhibition of HMG-CoA reductase.
Purification and properties of the catalytic domain of human 3-hydroxy-3-methylglutaryl-CoA reductase expressed in Escherichia coli.
Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis.
Isolation and structural characterization of a cDNA encoding Arabidopsis thaliana 3-hydroxy-3-methylglutaryl coenzyme A reductase.
Molecular cloning and sequence analysis of 3-hydroxy-3-methylglutaryl-coenzyme A reductase from the human parasite Schistosoma mansoni.
Regulation of HMG-CoA reductase: identification of the site phosphorylated by the AMP-activated protein kinase in vitro and in intact rat liver.
Identification of the principal catalytically important acidic residue of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
Aspects related to mevalonate biosynthesis in plants.
Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis.
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 422-888, AND SUBUNIT.