Literature summary for 1.1.1.34 extracted from

Oliveira, E.F.; Cerqueira, N.M.F.S.A.; Ramos, M.J.; Fernandes, P.A.
QM/MM study of the mechanism of reduction of 3-hydroxy-3-methylglutaryl coenzyme A catalyzed by human HMG-CoA reductase (2016), Catal. Sci. Technol., 6, 7172-7185.

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Crystallization (Commentary)

Crystallization (Comment)	Organism
analysis of the enzyme crystal structure (PDV ID 1DQA) at 2.0 A resolution	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
endoplasmic reticulum	-	Homo sapiens	5783	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
(R)-mevalonate + CoA + 2 NADP+	Homo sapiens	-	(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+	-	r

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P04035	-	-

Reaction

Reaction	Comment	Organism	Reaction ID
(R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+	reaction mechanism, modelling of three different systems, detailed overview. Formation of a mevaldyl-CoA intermediate protonated by a conserved active site lysine, Lys691. The conserved active site glutamate and aspartate residues, Glu559 and Asp767, along with the ribose moiety of NADPH, form a hydrogen bond network crucial to the increase of the stabilizing effect of Lys691 over the transition state. A charged His752 forms an oxyanion hole with Lys691 to stabilize the negative charge developed in the thioester oxygen	Homo sapiens	a

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
(R)-mevalonate + CoA + 2 NADP+	-	Homo sapiens	(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+	-	r

Subunits

Subunits	Comment	Organism
dimer	the catalytic portion of human HMG-CoA, after cleavage of the probable dimeric form found in the endoplasmic reticulum, 18 crystallized as a dimer of dimers. However, the dimer-dimer interface is distant from the active site and only the dimer of the molecule seems crucial for catalysis	Homo sapiens

Synonyms

Synonyms	Comment	Organism
HMG-CoA reductase	-	Homo sapiens
HMG-CoA-R	-	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
NADP+	-	Homo sapiens
NADPH	-	Homo sapiens

General Information

General Information	Comment	Organism
additional information	devlopment of three molecular models of human enzyme with different active site protonation states, and reaction mechanism analysis by molecular dynamics and quantum mechanics/molecular mechanics (QM/MM) calculations to detail the first reduction step, the rate-limiting step, of HMG-CoA-R	Homo sapiens

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Release 2023.1 (January 2023)