The Kdo biosynthetic pathway, substrate analogues and inhibitors

The Kdo biosynthetic pathway, substrate analogues and inhibitors. (a) The Kdo biosynthetic pathway. The enzymes involved are (1) arabinose-5-phosphate isomerase (API), (2) Kdo-8-phosphate (Kdo-8-P) synthase, (3) Kdo-8-P phosphatase and (4) cytidine 5′-monophosphate-Kdo synthetase. API catalyzes the reversible isomerization of d-ribulose 5-phosphate (Ru5P) to d-arabinose 5-phosphate (A5P) in the first step of Kdo biosynthesis. E. coli contains multiple paralogs of API genes including kdsD, kpsF and gutQ. The open-chain form and the ring form of A5P and Kdo-8-P are shown. PEP stands for phosphoenolpyruvate. The C1 and C2 atoms of A5P are marked with red asterisks. The C4 and C5 atoms of CMP-Kdo derived from C1 and C2 of A5P are also marked with red asterisks. (b) 5-Phospho-d-arabinonate (5PAA), a G6P substrate analog commonly used in enzyme mechanistic studies of PGI, is shown on the left. 4-Phospho-2,3-acetyl-d-erythrose hydroxamate (4PEH) was the most potent API inhibitor among the hydroxamate compounds tested in a study of F. tularensis KdsD (Yep et al., 2011).

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Structural analysis of arabinose-5-phosphate isomerase from Bacteroides fragilis and functional implications. (2014) Hsiu-Ju Chiu, et al. Acta Crystallogr D Biol Crystallogr. 2014 Oct 1;70(Pt 10):2640-2651. Figure: F1. All organisms Drosophila melanogaster Homo sapiens

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