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Architecture of microcin B17 synthetase: an octameric protein complex converting a ribosomally synthesized peptide into a DNA gyrase poison

DOI: 10.1016/j.molcel.2018.11.032 DOI Help

Authors: Dmitry Ghilarov (Skolkovo Institute of Science and Technology; Institute of Gene Biology of the Russian Academy of Sciences; Jagiellonian University) , Clare E. M. Stevenson (John Innes Centre) , Dmitrii Y. Travin (Institute of Science and Technology; Lomonosov Moscow State University) , Julia Piskunova (Skolkovo Institute of Science and Technology; Institute of Gene Biology of the Russian Academy of Sciences) , Marina Serebryakova (Skolkovo Institute of Science and Technology; Lomonosov Moscow State University) , Anthony Maxwell (Lomonosov Moscow State University) , David M. Lawson (John Innes Centre) , Konstantin Severinov (Skolkovo Institute of Science and Technology; Institute of Gene Biology of the Russian Academy of Sciences; Rutgers, The State University of New Jersey)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular Cell

State: Published (Approved)
Published: January 2019
Diamond Proposal Number(s): 9475 , 13467

Open Access Open Access

Abstract: The introduction of azole heterocycles into a peptide backbone is the principal step in the biosynthesis of numerous compounds with therapeutic potential. One of them is microcin B17, a bacterial topoisomerase inhibitor whose activity depends on the conversion of selected serine and cysteine residues of the precursor peptide to oxazoles and thiazoles by the McbBCD synthetase complex. Crystal structures of McbBCD reveal an octameric B4C2D2 complex with two bound substrate peptides. Each McbB dimer clamps the N-terminal recognition sequence, while the C-terminal heterocycle of the modified peptide is trapped in the active site of McbC. The McbD and McbC active sites are distant from each other, which necessitates alternate shuttling of the peptide substrate between them, while remaining tethered to the McbB dimer. An atomic-level view of the azole synthetase is a starting point for deeper understanding and control of biosynthesis of a large group of ribosomally synthesized natural products.

Journal Keywords: antibiotic; protein complex crystal structure; Escherichia coli microcin B17; DNA gyrase; RiPP; LAP; azole synthetase; cyclodehydratase; heterocyclase; dehydrogenase

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

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