5XK6

Structure of a prenyltransferase soaked with IPP

Summary for 5XK6

• Entry DOI: 10.2210/pdb5xk6/pdb
• Related: 5XK3 5XK7 5XK8 5XK9
• Descriptor: Undecaprenyl diphosphate synthase, MAGNESIUM ION, PYROPHOSPHATE 2-, ... (5 entities in total)
• Functional Keywords: prenyltransferase, antibiotic biosynthesis, transferase
• Biological source: Streptomyces sp. CNH189
• Total number of polymer chains: 4
• Total formula weight: 108370.09

Authors

Ko, T.P.,Guo, R.T.,Liu, W.,Chen, C.C.,Gao, J. (deposition date: 2017-05-05, release date: 2018-01-17, Last modification date: 2023-11-22)

Primary citation

Gao, J.,Ko, T.P.,Chen, L.,Malwal, S.R.,Zhang, J.,Hu, X.,Qu, F.,Liu, W.,Huang, J.W.,Cheng, Y.S.,Chen, C.C.,Yang, Y.,Zhang, Y.,Oldfield, E.,Guo, R.T.
"Head-to-Middle" and "Head-to-Tail" cis-Prenyl Transferases: Structure of Isosesquilavandulyl Diphosphate Synthase.
Angew. Chem. Int. Ed. Engl., 57:683-687, 2018

PubMed Abstract: 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 ζ 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° 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.

PubMed: 29215779
DOI: 10.1002/anie.201710185

Experimental method

X-RAY DIFFRACTION (1.58 Å)