| Type: | Domain | Name: | Hydroxymethylglutaryl-CoA reductase, class I/II, NAD/NADP-binding domain |
| Description: | There are two distinct classes of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase enzymes: class I consists of eukaryotic and most archaeal enzymes (), while class II consists of prokaryotic enzymes () [, ].Class I HMG-CoA reductases catalyse the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). In vertebrates, membrane-bound HMG-CoA reductase is the rate-limiting enzyme in the biosynthesis of cholesterol and other isoprenoids. In plants, mevalonate is the precursor of all isoprenoid compounds []. The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate, including cholesterol. In archaea, HMG-CoA reductase is a cytoplasmic enzyme involved in the biosynthesis of the isoprenoids side chains of lipids []. Class I HMG-CoA reductases consist of an N-terminal membrane domain (lacking in archaeal enzymes), and a C-terminal catalytic region. The catalytic region can be subdivided into three domains: an N-domain (N-terminal), a large L-domain, and a small S-domain (inserted within the L-domain). The L-domain binds the substrate, while the S-domain binds NADP.Class II HMG-CoA reductases catalyse the reverse reaction of class I enzymes, namely the NAD-dependent synthesis of HMG-CoA from mevalonate and CoA []. Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source. Class II enzymes lack a membrane domain. Their catalytic region is structurally related to that of class I enzymes, but it consists of only two domains: a large L-domain and a small S-domain (inserted within the L-domain). As with class I enzymes, the L-domain binds substrate, but the S-domain binds NAD (instead of NADP in class I).This entry represents the NADP or NAD binding S-domain found in class I and II enzymes, respectively. The S-domain has the same structural fold in both classes of enzymes, consisting of an alpha/beta sandwich with antiparallel beta sheets, with a (beta/alpha/beta)x2 topology []. | Short Name: | HMG_CoA_Rdtase_NAD(P)-bd_dom |
