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Structural Analysis of Mevalonate-3-Kinase Provides Insight Into The Mechanisms of Isoprenoid Pathway Decarboxylases.

Protein Sci.. 2014-11; 
Vinokur JM, Korman TP, Sawaya MR, Collazo M, Cascio D, Bowie JU. 659 Boyer Hall University of California - Los Angeles 611 Charles E. Young Dr. East Los Angeles, CA 90095-1570 (310) 206-4747.
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摘要

In animals, cholesterol is made from 5-carbon building blocks produced by the mevalonate pathway. Drugs that inhibit the mevalonate pathway such as atorvastatin (Lipitor) have led to successful treatments for high cholesterol in humans. Another potential target for the inhibition of cholesterol synthesis is mevalonate diphosphate decarboxylase (MDD), which catalyzes the phosphorylation of (R)-mevalonate diphosphate, followed by decarboxylation to yield isopentenyl pyrophosphate. We recently discovered an MDD homolog, mevalonate-3-kinase (M3K) from Thermoplasma acidophilum, which catalyzes the identical phosphorylation of (R)-mevalonate, but without concomitant decarboxylation. Thus, M3K catalyzes half the react... More

关键词

Cholesterol; GHMP kinase; Mevalonate Diphosphate Decarboxylase; Mevalonate Kinase; Mevalonate Pathway; Mevalonate Pyrophosphate Decarboxylase; Mevalonate-3-Kinase; Statin