HMG COA REDUCTASE

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3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) catalyzes the committed step in the biosynthesis of isoprenoids and steroids such as vitamin D and cholesterol. HMG-CoA reductase is the target of inhibitors, which present a first choice in cholesterol lowering medication. We have obtained well diffracting crystals of the catalytic domain of human HMG-CoS reductase. Although the structure of a homolog to mammalian HMG-CoA reductase from Pseudomonas mevalonii has been solved, the sequence identity to human reductase is only 20% and a molecular replacement solution has not yet been found. We intend to collect MAD data using seleno-methionine crystals to help solve the structure of the catalytic domain of human HMG-CoA reductase.