The mevalonate pathway synthesizes the precursors of isoprenoids, the largest and most structurally diverse class of natural products, many of which are used as drugs for the treatment of human diseases. Catalyzing the committed and rate-limiting step of the mevalonate pathway, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR) reduces HMG-CoA to mevalonate using two equivalents of NAD(P)H. To optimize isoprenoid production, greater structural and mechanistic understanding of HMGR is necessary. HMGR has evolved into class I HMGRs, which are found in eukaryotes and in some bacteria and archaea and utilize NADPH exclusively, and class II HMGRs, which are found only in bacteria and archaea and whose cofactor preferences vary. To better understand the structural basis of cofactor specificity, we studied the class II HMGRs from <i>Enterococcus faecalis</i> (EfHMGR), which prefers NADPH, and <i>Bordetella petrii</i> (BpHMGR), which prefers NADH. Mutant constructs were also studied to more closely examine specific regions of the enzymes and determine their contributions to cofactor specificity. After these proteins were expressed, purified, kinetically characterized, and crystallized, the structures and cofactor specificities of the wild-type and mutant constructs were examined.

Investigating the structural basis of HMG-CoA reductase cofactor specificity

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.