Human serine racemase structure/activity relationship studies provide mechanistic insight and point to position 84 as a hot spot for β-elimination function.

ABSTRACT: There is currently great interest in human serine racemase, the enzyme responsible for producing the NMDA co-agonist d-serine. Reported correlation of d-serine levels with disorders including Alzheimer's disease, ALS, and ischemic brain damage (elevated d-serine) and schizophrenia (reduced d-serine) has further piqued this interest. Reported here is a structure/activity relationship study of position Ser⁸⁴, the putative re-face base. In the most extreme case of functional reprogramming, the S84D mutant displays a dramatic reversal of β-elimination substrate specificity in favor of l-serine over the normally preferred l-serine-O-sulfate (∼1200-fold change in k_cat/K_m ratios) and l (l-THA; ∼5000-fold change in k_cat

SUBMITTER: Nelson DL 

PROVIDER: S-EPMC5572919 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature