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Publication Abstract from PubMed

Radical S-adenosyl-L-methionine (SAM) enzymes couple the reductive cleavage of SAM to radical-mediated transformations that have proven to be quite broad in scope. DesII is one such enzyme from the biosynthetic pathway of TDP-desosamine where it catalyzes a radical-mediated deamination. Previous studies have suggested that this reaction proceeds via direct elimination of ammonia from an alpha-hydroxyalkyl radical or its conjugate base (i.e., a ketyl radical) rather than 1,2-migration of the amino group to form a carbinolamine radical intermediate. However, without a crystal structure, the active site features responsible for this chemistry have remained largely unknown. The crystallographic studies described herein help to fill this gap by providing a structural description of the DesII active site. Computational analyses based on the solved crystal structure are consistent with direct elimination and indicate that an active site glutamate residue likely serves as a general base to promote deprotonation of the alpha-hydroxyalkyl radical intermediate and elimination of the ammonia group.

Mechanistic Insights from the Crystal Structure and Computational Analysis of the Radical SAM Deaminase DesII.,Hou X, Feng J, Franklin JL, Russo R, Guo Z, Zhou J, Gao JM, Liu HW, Wang B Adv Sci (Weinh). 2024 Jun 28:e2403494. doi: 10.1002/advs.202403494. PMID:38943270^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.