Crystallization (Comment) | Organism |
---|---|
analysis of the enzyme crystal structure (PDV ID 1DQA) at 2.0 A resolution | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
endoplasmic reticulum | - |
Homo sapiens | 5783 | - |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P04035 | - |
- |
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 |
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 | 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 | Comment | Organism |
---|---|---|
HMG-CoA reductase | - |
Homo sapiens |
HMG-CoA-R | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADP+ | - |
Homo sapiens | |
NADPH | - |
Homo sapiens |
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 |