8HZY

The crystal structure of a Radical SAM Enzyme DesII

Summary for 8HZY

• Entry DOI: 10.2210/pdb8hzy/pdb
• Descriptor: DesII, IRON/SULFUR CLUSTER, METHIONINE, ... (4 entities in total)
• Functional Keywords: radical s-adenosyl-l-methionine enzyme, deamination, dehydrogenase, biosynthetic protein
• Biological source: Homo sapiens
• Total number of polymer chains: 2
• Total formula weight: 113367.94

Authors

Hou, X.L.,Zhou, J.H. (deposition date: 2023-01-10, release date: 2024-07-10, Last modification date: 2024-10-16)

Primary citation

Hou, X.,Feng, J.,Franklin, J.L.,Russo, R.,Guo, Z.,Zhou, J.,Gao, J.M.,Liu, H.W.,Wang, B.
Mechanistic Insights from the Crystal Structure and Computational Analysis of the Radical SAM Deaminase DesII.
Adv Sci, 11:e2403494-e2403494, 2024

PubMed Abstract: 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 α-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 α-hydroxyalkyl radical intermediate and elimination of the ammonia group.

PubMed: 38943270
DOI: 10.1002/advs.202403494

Experimental method

X-RAY DIFFRACTION (2.03978804974 Å)