Utilizing a pH-dependent reaction triggering method to elucidate the mechanism of bacterial HMG-CoA reductase using time-resolved crystallography

HMG-CoA reductase in Pseudomonas mevalonii (PmHMGR) utilizes the co-substrates mevalonate and coenzyme-A (CoA) and 2 NAD+ cofactors to generate HMG-CoA. Having shown to be an essential enzyme for the survival of gram-positive antibiotic resistant pathogenic bacteria, studying its mechanism in detail will be beneficial in developing novel antibacterials. Details about this mechanism such as the conformational changes that allow intermediate formation, the cofactor exchange at the active site and product release remain unknown.