PMP–diketopiperazine adducts form at the active site of a PLP dependent enzyme involved in formycin biosynthesis

Sisi Gao; Huanting Liu; Valérie de Crécy-Lagard; Wen Zhu; Nigel G. J. Richards; James H. Naismith

doi:10.1039/C9CC06975E

PMP–diketopiperazine adducts form at the active site of a PLP dependent enzyme involved in formycin biosynthesis†

Sisi Gao,

^ab Huanting Liu,

^b Valérie de Crécy-Lagard,

^c Wen Zhu,

^d Nigel G. J. Richards

^ef and James H. Naismith

*^ghi

Author affiliations

* Corresponding authors

^a Research Complex at Harwell, Didcot, UK

^b BSRC, University of St Andrews, St Andrews, UK

^c Department of Microbiology, University of Florida, Gainesville, FL 32611, USA

^d Department of Chemistry and California, Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA

^e School of Chemistry, Cardiff University, Park Place, Cardiff, UK

^f Foundation for Applied Molecular Evolution, Alachua, FL 32415, USA

^g Division of Structural Biology, University of Oxford, Oxford, UK
E-mail: naismith@strubi.ox.ac.uk

^h The Rosalind Franklin Institute, Didcot, UK

ⁱ State Key Laboratory of Biotherapy, University of Sichuan, China

Abstract

ForI is a PLP-dependent enzyme from the biosynthetic pathway of the C-nucleoside antibiotic formycin. Cycloserine is thought to inhibit PLP-dependent enzymes by irreversibly forming a PMP–isoxazole. We now report that ForI forms novel PMP–diketopiperazine derivatives following incubation with both D and L cycloserine. This unexpected result suggests chemical diversity in the chemistry of cycloserine inhibition.

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DOI: https://doi.org/10.1039/C9CC06975E
Article type: Communication
Submitted: 06 Sep 2019
Accepted: 16 Oct 2019
First published: 15 Nov 2019
This article is Open Access

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Chem. Commun., 2019,55, 14502-14505

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PMP–diketopiperazine adducts form at the active site of a PLP dependent enzyme involved in formycin biosynthesis

S. Gao, H. Liu, V. de Crécy-Lagard, W. Zhu, N. G. J. Richards and J. H. Naismith, Chem. Commun., 2019, 55, 14502 DOI: 10.1039/C9CC06975E

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Chemical Communications

PMP–diketopiperazine adducts form at the active site of a PLP dependent enzyme involved in formycin biosynthesis†

Abstract

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PMP–diketopiperazine adducts form at the active site of a PLP dependent enzyme involved in formycin biosynthesis

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