English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

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

MPS-Authors
/persons/resource/persons254801

Voegeli,  Bastian
Understanding and Building Metabolism, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

/persons/resource/persons254714

Shima,  Seigo
Department-Independent Research Group Microbial Protein Structure, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

/persons/resource/persons254247

Erb,  Tobias J.
Understanding and Building Metabolism, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

/persons/resource/persons256582

Wagner,  Tristan
Department-Independent Research Group Microbial Protein Structure, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

External Resource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Voegeli, B., Shima, S., Erb, T. J., & Wagner, T. (2019). Crystal structure of archaeal HMG-CoA reductase: insights into structural changes of the C-terminal helix of the class-I enzyme. FEBS LETTERS, 593(5), 543-553. doi:10.1002/1873-3468.13331.


Cite as: http://hdl.handle.net/21.11116/0000-0008-D638-8
Abstract
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 (L alpha 10-11) 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.