Uncovering the chemistry of C-C bond formation in C-nucleoside biosynthesis: crystal structure of a C-glycoside synthase/PRPP complex

Sisi Gao; Ashish Radadiya; Wenbo Li; Huanting Liu; Wen Zhu; Valérie de Crécy-Lagard; Nigel G J Richards; James H Naismith

doi:10.1039/d0cc02834g

Uncovering the chemistry of C-C bond formation in C-nucleoside biosynthesis: crystal structure of a C-glycoside synthase/PRPP complex

Chem Commun (Camb). 2020 Jul 14;56(55):7617-7620. doi: 10.1039/d0cc02834g. Epub 2020 Jun 9.

Authors

Sisi Gao¹, Ashish Radadiya², Wenbo Li³, Huanting Liu⁴, Wen Zhu⁵, Valérie de Crécy-Lagard⁶, Nigel G J Richards⁷, James H Naismith⁸

Affiliations

¹ Research Complex at Harwell, Didcot, OX11 0FA, UK and BSRC, University of St Andrews, St Andrews, KY16 9ST, UK.
² School of Chemistry, Cardiff University, Cardiff, CF10 3AT, UK.
³ Division of Structural Biology, University of Oxford, Oxford, OX3 7BN, UK. naismith@strubi.ox.ac.uk.
⁴ BSRC, University of St Andrews, St Andrews, KY16 9ST, UK.
⁵ Department of Chemistry and California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA.
⁶ Department of Microbiology, University of Florida, Gainesville, FL 32611, USA.
⁷ School of Chemistry, Cardiff University, Cardiff, CF10 3AT, UK and Foundation for Applied Molecular Evolution, Alachua, FL 32615, USA.
⁸ Division of Structural Biology, University of Oxford, Oxford, OX3 7BN, UK. naismith@strubi.ox.ac.uk and The Rosalind Franklin Institute, Didcot, OX11 0FA, UK.

Abstract

The enzyme ForT catalyzes C-C bond formation between 5'-phosphoribosyl-1'-pyrophosphate (PRPP) and 4-amino-1H-pyrazole-3,5-dicarboxylate to make a key intermediate in the biosynthesis of formycin A 5'-phosphate by Streptomyces kaniharaensis. We report the 2.5 Å resolution structure of the ForT/PRPP complex and locate active site residues critical for PRPP recognition and catalysis.

MeSH terms

Bacterial Proteins / chemistry
Bacterial Proteins / metabolism
Biocatalysis
Carbon-Carbon Ligases / chemistry
Carbon-Carbon Ligases / metabolism*
Catalytic Domain
Crystallography, X-Ray
Models, Chemical
Phosphoribosyl Pyrophosphate / chemistry
Phosphoribosyl Pyrophosphate / metabolism*
Protein Binding
Streptomyces / enzymology

Substances

Bacterial Proteins
Phosphoribosyl Pyrophosphate
Carbon-Carbon Ligases

Supplementary concepts

Streptomyces kaniharaensis

Grants and funding

R01 GM129793/GM/NIGMS NIH HHS/United States