5xk6

Publication Abstract from PubMed

We report the first X-ray crystallographic structure of the "head-to-middle" prenyltransferase, isosesquilavandulyl diphosphate synthase, involved in biosynthesis of the merochlorin class of antibiotics. The protein adopts the zeta or cis-prenyl transferase fold but remarkably, unlike tuberculosinol adenosine synthase and other cis-prenyl transferases (e.g. cis-farnesyl, decaprenyl, undecaprenyl diphosphate synthases), the large, hydrophobic side chain does not occupy a central hydrophobic tunnel. Instead, it occupies a surface pocket oriented at 90 degrees to the hydrophobic tunnel. Product chain-length control is achieved by squeezing out the ligand from the conventional allylic S1 binding site, with proton abstraction being achieved using a diphosphate-Asn-Ser relay. The structures revise and unify our thinking as to the mechanism of action of many other prenyl transferases and may also be of use in engineering new merochlorin-class antibiotics.

"Head-to-Middle" and "Head-to-Tail" cis-Prenyl Transferases: Structure of Isosesquilavandulyl Diphosphate Synthase.,Gao J, Ko TP, Chen L, Malwal SR, Zhang J, Hu X, Qu F, Liu W, Huang JW, Cheng YS, Chen CC, Yang Y, Zhang Y, Oldfield E, Guo RT Angew Chem Int Ed Engl. 2018 Jan 15;57(3):683-687. doi: 10.1002/anie.201710185., Epub 2017 Dec 21. PMID:29215779^[1]

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