| Type: | Active_site | Name: | Hydroxymethylglutaryl-coenzyme A synthase, active site |
| Description: | Hydroxymethylglutaryl-CoA synthase () catalyses the condensation of acetyl-CoA with acetoacetyl-CoA to produce HMG-CoA and CoA, the second reaction in the mevalonate-dependent isoprenoid biosynthesis pathway. HMG-CoA synthase contains an important catalytic cysteine residue that acts as a nucleophile in the first step of the reaction: the acetylation of the enzyme by acetyl-CoA (its first substrate) to produce an acetyl-enzyme thioester, releasing the reduced coenzyme A. The subsequent nucleophilic attack on acetoacetyl-CoA (its second substrate) leads to the formation of HMG-CoA [].HMG-CoA synthase occurs in eukaryotes, archaea and certain bacteria []. In vertebrates, there are two isozymes located in different subcellular compartments: a cytosolic form that is the starting point of the mevalonate pathway (leads to cholesterol and other sterolic and isoprenoid compounds), and a mitochondrial form responsible for ketone body biosynthesis. HMG-CoA is also found in other eukaryotes such as insects, plants and fungi []. In bacteria, isoprenoid precursors are generally synthesised via an alternative, non-mevalonate pathway, however a number of Gram-positive pathogens utilise a mevalonate pathway involving HMG-CoA synthase that is parallel to that found in eukaryotes [, ].This entry represents the sequence surrounding the catalytic cysteine required for nucleophilic attack in the first step of the reaction, the acetylation of the enzyme by acetyl-CoA. | Short Name: | HMG_CoA_synt_AS |
