Structural highlights
Publication Abstract from PubMed
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.
1,2-diol dehydration by the radical SAM enzyme AprD4 - a matter of proton circulation and substrate flexibility.,Liu WQ, Amara P, Mouesca JM, Ji X, Renoux O, Martin L, Zhang C, Zhang Q, Nicolet Y J Am Chem Soc. 2018 Jan 4. doi: 10.1021/jacs.7b10501. PMID:29300094[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liu WQ, Amara P, Mouesca JM, 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. 2018 Jan 4. doi: 10.1021/jacs.7b10501. PMID:29300094 doi:http://dx.doi.org/10.1021/jacs.7b10501
