7VOB

The crystal structure of a Radical SAM Enzyme BlsE involved in the Biosynthesis of Blasticidin S

Summary for 7VOB

• Entry DOI: 10.2210/pdb7vob/pdb
• Descriptor: Cytosylglucuronate decarboxylase, IRON/SULFUR CLUSTER, S-ADENOSYLMETHIONINE, ... (6 entities in total)
• Functional Keywords: radical sam enzyme, dehydratase, blasticidin s, biosynthetic protein
• Biological source: Streptomyces griseochromogenes
• Total number of polymer chains: 1
• Total formula weight: 41656.76

Authors

Hou, X.L.,Zhou, J.H. (deposition date: 2021-10-13, release date: 2022-05-04, Last modification date: 2024-05-29)

Primary citation

Lee, Y.H.,Hou, X.,Chen, R.,Feng, J.,Liu, X.,Ruszczycky, M.W.,Gao, J.M.,Wang, B.,Zhou, J.,Liu, H.W.
Radical S -Adenosyl Methionine Enzyme BlsE Catalyzes a Radical-Mediated 1,2-Diol Dehydration during the Biosynthesis of Blasticidin S.
J.Am.Chem.Soc., 144:4478-4486, 2022

PubMed Abstract: The biosynthesis of blasticidin S has drawn attention due to the participation of the radical -adenosyl methionine (SAM) enzyme BlsE. The original assignment of BlsE as a radical-mediated, redox-neutral decarboxylase is unusual because this reaction appears to serve no biosynthetic purpose and would need to be reversed by a subsequent carboxylation step. Furthermore, with the exception of BlsE, all other radical SAM decarboxylases reported to date are oxidative in nature. Careful analysis of the BlsE reaction, however, demonstrates that BlsE is not a decarboxylase but instead a lyase that catalyzes the dehydration of cytosylglucuronic acid (CGA) to form cytosyl-4'-keto-3'-deoxy-d-glucuronic acid, which can rapidly decarboxylate nonenzymatically . Analysis of substrate isotopologs, fluorinated analogues, as well as computational models based on X-ray crystal structures of the BlsE·SAM (2.09 Å) and BlsE·SAM·CGA (2.62 Å) complexes suggests that BlsE catalysis likely proceeds via direct elimination of water from the CGA C4' α-hydroxyalkyl radical as opposed to 1,2-migration of the C3'-hydroxyl prior to dehydration. Biosynthetic and mechanistic implications of the revised assignment of BlsE are discussed.

PubMed: 35238201
DOI: 10.1021/jacs.1c12010

Experimental method

X-RAY DIFFRACTION (2.09224113188 Å)