HMG-CoA reductase family
| Hydroxymethylglutaryl-coenzyme A reductase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 complex of the catalytic portion of human hmg-coa reductase with compactin (also known as mevastatin) | |||||||||
| Identifiers | |||||||||
| Symbol | HMG-CoA_red | ||||||||
| Pfam | PF00368 | ||||||||
| InterPro | IPR002202 | ||||||||
| PROSITE | PDOC00064 | ||||||||
| SCOP2 | 1qax / SCOPe / SUPFAM | ||||||||
| |||||||||
In molecular biology, the HMG-CoA reductase family is a family of enzymes which participate in the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids.
There are two distinct classes of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase enzymes: class I consists of eukaryotic and most archaeal enzymes EC 1.1.1.34, while class II consists of prokaryotic enzymes EC 1.1.1.88.[1][2]
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.[2] 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.[3] 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.[4] 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).
References
- ^ Bochar DA, Stauffacher CV, Rodwell VW (February 1999). "Sequence comparisons reveal two classes of 3-hydroxy-3-methylglutaryl coenzyme A reductase". Mol. Genet. Metab. 66 (2): 122–7. doi:10.1006/mgme.1998.2786. PMID 10068515.
- ^ a b Friesen JA, Rodwell VW (2004). "The 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductases". Genome Biol. 5 (11): 248. doi:10.1186/gb-2004-5-11-248. PMC 545772. PMID 15535874.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Kim DY, Bochar DA, Stauffacher CV, Rodwell VW (December 1999). "Expression and characterization of the HMG-CoA reductase of the thermophilic archaeon Sulfolobus solfataricus". Protein Expr. Purif. 17 (3): 435–42. doi:10.1006/prep.1999.1147. PMID 10600463.
- ^ Hedl M, Tabernero L, Stauffacher CV, Rodwell VW (April 2004). "Class II 3-hydroxy-3-methylglutaryl coenzyme A reductases". J. Bacteriol. 186 (7): 1927–32. doi:10.1128/jb.186.7.1927-1932.2004. PMC 374403. PMID 15028676.