ArticleThe Biochemical journal2000
Characterization and regulation of Leishmania major 3-hydroxy-3-methylglutaryl-CoA reductase.
Article in The Biochemical journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Simvastatin Resistance ofMicroorganisms · 2022Article
- Unravelling the myth surrounding sterol biosynthesis as plausible target for drug design against leishmaniasis.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2021Review
- Topical Simvastatin as Host-Directed Therapy against Severity of Cutaneous Leishmaniasis in Mice.Scientific reports · 2016Article
- Antileishmanial effect of mevastatin is due to interference with sterol metabolism.Parasitology research · 2015Article
- Induction of mitochondrial dysfunction and oxidative stress in Leishmania donovani by orally active clerodane diterpene.Antimicrobial agents and chemotherapy · 2014Article
- Ketanserin, an antidepressant, exerts its antileishmanial action via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) enzyme of Leishmania donovani.Parasitology research · 2014Article
- Chemical and genetic validation of the statin drug target to treat the helminth disease, schistosomiasis.PloS one · 2014Article
- Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and application of statins as a novel effective therapeutic approach against Acanthamoeba infections.Antimicrobial agents and chemotherapy · 2013Article
- Atorvastatin as a potential anti-malarial drug: in vitro synergy in combinational therapy with quinine against Plasmodium falciparum.Malaria journal · 2010Article
- Statins as potential antimalarial drugs: low relative potency and lack of synergy with conventional antimalarial drugs.Antimicrobial agents and chemotherapy · 2009Article
- Atorvastatin is 10-fold more active in vitro than other statins against Plasmodium falciparum.Antimicrobial agents and chemotherapy · 2007Article
- Antileishmanial activity of the terpene nerolidol.Antimicrobial agents and chemotherapy · 2005Article
- Mitochondrial localization of the mevalonate pathway enzyme 3-Hydroxy-3-methyl-glutaryl-CoA reductase in the Trypanosomatidae.Molecular biology of the cell · 2004Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In eukaryotes the enzyme 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase catalyses the synthesis of mevalonic acid, a common precursor to all isoprenoid compounds. Here we report the isolation and overexpression of the gene coding for HMG-CoA reductase from Leishmania major. The protein from Leishmania lacks the membrane domain characteristic of eukaryotic cells but exhibits sequence similarity with eukaryotic reductases. Highly purified protein was achieved by ammonium sulphate precipitation followed by chromatography on hydroxyapatite. Kinetic parameters were determined for the protozoan reductase, obtaining K(m) values for the overall reaction of 40.3+/-5.8 microM for (R,S)-HMG-CoA and 81.4+/-5.3 microM for NADPH; V(max) was 33.55+/-1.8 units x mg(-1). Gel-filtration experiments suggested an apparent molecular mass of 184 kDa with subunits of 46 kDa. Finally, in order to achieve a better understanding of the role of this enzyme in trypanosomatids, the effect of possible regulators of isoprenoid biosynthesis in cultured promastigote cells was studied. Neither mevalonic acid nor serum sterols appear to modulate enzyme activity whereas incubation with lovastatin results in significant increases in the amount of reductase protein. Western- and Northern-blot analyses indicate that this activation is apparently performed via post-transcriptional control.
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