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HMGCR dimer binds statins
Stable Identifier
R-HSA-9705584
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
,
endoplasmic reticulum membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
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Metabolism (Homo sapiens)
Metabolism of lipids (Homo sapiens)
Metabolism of steroids (Homo sapiens)
Cholesterol biosynthesis (Homo sapiens)
HMGCR dimer binds statins (Homo sapiens)
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Dimeric 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR dimer) is the key enzyme in the cholesterol biosynthetic pathway and catalyzes the committed step of the reduction of beta-hydroxy-3-methylglutaryl CoA (bHMG-CoA) to mevalonate. HMGCR is regarded as one of the most important drug targets in the treatment of hypercholesterolemia. HMGCR inhibitors, commonly referred to as statins, are among the most widely prescribed drugs in the world. Statins work by their similarity to the substrate (bHMG-CoA), leading to competition towards the HMG binding site on the enzyme between substrate and statins (Istvan & Deisenhofer 2001). As statins also block the access of the substrate to the binding site, the affinity of HMGCR for statins is slightly higher than its affinity for the substrate (Istvan 2002, Carbonell & Ernesto Freire 2005, Gesto et al. 2020). Statins can be divided in two types, according to their origin. Type I statins e.g. lovastatin, pravastatin and simvastatin, are natural fungal products and Type II statins e.g. atorvastatin, rosuvastatin and fluvastatin, are fully synthetic.
Literature References
PubMed ID
Title
Journal
Year
12486413
Structural mechanism for statin inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase
Istvan, ES
Am Heart J
2002
16128575
Binding thermodynamics of statins to HMG-CoA reductase
Freire, E
,
Carbonell, T
Biochemistry
2005
11349148
Structural mechanism for statin inhibition of HMG-CoA reductase
Istvan, ES
,
Deisenhofer, J
Science
2001
Participants
Input
HMGCR dimer [endoplasmic reticulum membrane]
(Homo sapiens)
statins [cytosol]
Output
HMGCR dimer:statins [endoplasmic reticulum membrane]
(Homo sapiens)
Participates
as an event of
Cholesterol biosynthesis (Homo sapiens)
Orthologous Events
HMGCR dimer binds statins (Bos taurus)
HMGCR dimer binds statins (Caenorhabditis elegans)
HMGCR dimer binds statins (Canis familiaris)
HMGCR dimer binds statins (Danio rerio)
HMGCR dimer binds statins (Dictyostelium discoideum)
HMGCR dimer binds statins (Drosophila melanogaster)
HMGCR dimer binds statins (Gallus gallus)
HMGCR dimer binds statins (Mus musculus)
HMGCR dimer binds statins (Rattus norvegicus)
HMGCR dimer binds statins (Saccharomyces cerevisiae)
HMGCR dimer binds statins (Schizosaccharomyces pombe)
HMGCR dimer binds statins (Sus scrofa)
HMGCR dimer binds statins (Xenopus tropicalis)
Authored
Jassal, B (2020-10-27)
Reviewed
Huddart, R (2022-03-01)
Created
Jassal, B (2020-10-27)
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