Human hydroxymethylglutaryl-coenzyme A reductase (HMGCR) and statin sensitivity.

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dc.contributor.authorJawaid, Safdar
dc.contributor.authorGertz, Monica
dc.contributor.authorCorsino, Carlin
dc.contributor.authorCheung, Jamie
dc.contributor.authorSeidle, Heather
dc.contributor.authorCouch, Robin D
dc.date.accessioned2011-11-15T04:23:03Z
dc.date.available2011-11-15T04:23:03Z
dc.date.issued2010-12
dc.description.abstractWhile statins, hydroxymethylglutaryl-coenzyme A reductase (HMGCR) inhibitors, are clinically proven to reduce plasma cholesterol levels, a wide variation in inter-individual response to statin therapy has been observed. Pharmacogenetic studies have identified multiple loci that potentially contribute towards the statin response, including the HMGCR gene. To examine, if a statin-resistant, catalytically-active isoform of the human HMGCR could be generated, we have rationally altered the protein to include additional residues in the flap domain, which has a role in statin binding. Comparative enzyme assays with purified wild-type and mutant isoforms reveal the alteration imposes a slight (38%) decrease in the for the substrate, a near 2-fold increase in turnover number, and a 480% increase in the Ki for lovastatin. Thus, alterations in HMGCR could contribute towards the synergistic effects of multiple loci in the statin response.en_US
dc.identifier.citationJawaid Safdar, Gertz Monica, Corsino Carlin, Cheung Jamie, Seidle Heather, Couch Robin D. Human hydroxymethylglutaryl-coenzyme A reductase (HMGCR) and statin sensitivity. Indian Journal of Biochemistry & Biophysics. 2010 Dec; 47(6): 331-339.en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/135284
dc.language.isoenen_US
dc.source.urihttps://nopr.niscair.res.in/bitstream/123456789/10855/1/IJBB%2047%286%29%20331-339.pdfen_US
dc.subjectHMGCRen_US
dc.subjectHydroxymethylglutaryl-coenzyme A reductaseen_US
dc.subjectLovastatinen_US
dc.subjectHypercholesterolemiaen_US
dc.subject.meshAmino Acid Sequence
dc.subject.meshBase Sequence
dc.subject.meshDNA Primers --genetics
dc.subject.meshHumans
dc.subject.meshHydroxymethylglutaryl CoA Reductases --chemistry
dc.subject.meshHydroxymethylglutaryl CoA Reductases --genetics
dc.subject.meshHydroxymethylglutaryl CoA Reductases --metabolism
dc.subject.meshHydroxymethylglutaryl-CoA Reductase Inhibitors --pharmacology
dc.subject.meshKinetics
dc.subject.meshModels, Molecular
dc.subject.meshMolecular Sequence Data
dc.subject.meshMutagenesis
dc.subject.meshPharmacogenetics
dc.subject.meshProtein Engineering
dc.subject.meshRecombinant Proteins --chemistry
dc.subject.meshRecombinant Proteins --genetics
dc.subject.meshRecombinant Proteins --metabolism
dc.subject.meshSequence Homology, Amino Acid
dc.titleHuman hydroxymethylglutaryl-coenzyme A reductase (HMGCR) and statin sensitivity.en_US
dc.typeArticleen_US
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