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

Sisi Gao,Nigel G J Richards,Valérie De Crécy-Lagard,Wen Zhu,James H Naismith,Huanting Liu

doi:10.1039/c9cc06975e

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.

Highlights

Sisi Gao, ab Huanting Liu, b Valerie de Crecy-Lagard, c Wen Zhu, d Nigel G
ForI is a pyridoxal 50-phosphate (PLP)-dependent enzyme from the biosynthetic pathway of the C-nucleoside antibiotic formycin
We report that ForI forms novel pyridoxamine 50-phosphate (PMP)–diketopiperazine derivatives following incubation with both D and L cycloserine

Summary

Introduction

Sisi Gao, ab Huanting Liu, b Valerie de Crecy-Lagard, c Wen Zhu, d Nigel G. In each external aldimine complex, the atoms of the diketopiperazine adduct originating from PLP adopt the same positions as observed for the PMP structure.

Results

Conclusion