Crystal structure of archaeal HMG-CoA reductase: insights into structural changes of the C-terminal helix of the class-I enzyme

FEBS Letters

article

Bastian Vögeli¹  Seigo Shima²  Tobias J. Erb¹  Tristan Wagner² 

[1] Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology;Microbial Protein Structure Group, Max Planck Institute for Terrestrial Microbiology

关键词: cholesterol biosynthesis;    isoprenoids;    mevalonate biosynthesis;    statins;    structural rearrangement;    X-ray crystallography;   

DOI  :  10.1002/1873-3468.13331

来源: John Wiley & Sons Ltd.

【 摘 要 】

3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) catalyses the last step in mevalonate biosynthesis. HMGR is the target of statin inhibitors that regulate cholesterol concentration in human blood. Here, we report the properties and structures of HMGR from an archaeon Methanothermococcus thermolithotrophicus (mHMGR). The structures of the apoenzyme and the NADPH complex are highly similar to those of human HMGR. A notable exception is C-terminal helix (La10-11) that is straight in both mHMGR structures. This helix is kinked and closes the active site in the human enzyme ternary complex, pointing to a substrate-induced structural rearrangement of C-terminal in class-I HMGRs during the catalytic cycle.

【 授权许可】

Unknown