6FD2

Radical SAM 1,2-diol dehydratase AprD4 in complex with its substrate paromamine

Summary for 6FD2

• Entry DOI: 10.2210/pdb6fd2/pdb
• Descriptor: Putative apramycin biosynthetic oxidoreductase 4, paromamine, IRON/SULFUR CLUSTER, ... (6 entities in total)
• Functional Keywords: radical sam, fes-cluster containing enzyme, 1, 2-diol dehydratase, biosynthetic protein
• Biological source: Streptoalloteichus tenebrarius (strain ATCC 17920 / DSM 40477 / NCIB 11028) (Streptomyces tenebrarius)
• Total number of polymer chains: 2
• Total formula weight: 102915.54

Authors

Liu, W.Q.,Amara, P.,Mouesca, J.M.,Ji, X.,Renoux, O.,Martin, L.,Zhang, C.,Zhang, Q.,Nicolet, Y. (deposition date: 2017-12-21, release date: 2018-01-17, Last modification date: 2024-01-17)

Primary citation

Liu, W.Q.,Amara, P.,Mouesca, J.M.,Ji, X.,Renoux, O.,Martin, L.,Zhang, C.,Zhang, Q.,Nicolet, Y.
1,2-Diol Dehydration by the Radical SAM Enzyme AprD4: A Matter of Proton Circulation and Substrate Flexibility.
J. Am. Chem. Soc., 140:1365-1371, 2018

PubMed Abstract: Regiospecific dehydration of vicinal diols by enzymes is a difficult reaction that usually requires activation by dedicated organic cofactors. The enzymatic use of radical-based chemistry is an effective but challenging alternative as radical intermediates are difficult to control. Here we report the X-ray structure of the radical S-adenosyl-l-methionine (SAM) dehydratase AprD4 involved in the biosynthesis of the aminoglycoside (AG) antibiotic apramycin. Using in vitro characterizations and theoretical calculations based on our crystal structure, we have been able to propose a detailed mechanism of AprD4 catalysis, which involves a complex partially substrate-induced proton relay network in the enzyme active site and highlights the key role of the protein matrix in driving high-energy intermediates.

PubMed: 29300094
DOI: 10.1021/jacs.7b10501

Experimental method

X-RAY DIFFRACTION (2.55 Å)