Conserved Site

Hydroxymethylglutaryl-CoA reductase, class I/II, conserved site (IPR023076)

Short name: HMG_CoA_Rdtase_CS


There are two distinct classes of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase enzymes: class I consists of eukaryotic and most archaeal enzymes (EC:, while class II consists of prokaryotic enzymes (EC: [PMID: 10068515, PMID: 15535874].

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 [PMID: 15535874]. 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 [PMID: 10600463]. 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 [PMID: 15028676]. 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 three conserved sites found in HMG-CoA reductases. The first is located in the centre of the catalytic domain, the second is a glycine-rich region located in the C-terminal section of the same catalytic domain and the third is also located in the C-terminal section and contains an histidine residue that appears to be implicated in the catalytic mechanism as a general base [PMID: 2656635].

GO terms

Biological Process

GO:0055114 oxidation-reduction process

Molecular Function

GO:0004420 hydroxymethylglutaryl-CoA reductase (NADPH) activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns
PROSITE patterns
PROSITE patterns