6CI5

Crystal structure of the formyltransferase PseJ from Anoxybacillus kamchatkensis in complex with UDP-4,6-dideoxy-4-formamido-L-AltNAc and tetrahydrofolate

Summary for 6CI5

• Entry DOI: 10.2210/pdb6ci5/pdb
• Descriptor: formyltransferase PseJ, SULFATE ION, (2R,3R,4S,5R,6S)-3-(acetylamino)-5-(formylamino)-4-hydroxy-6-methyltetrahydro-2H-pyran-2-yl [(2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl dihydrogen diphosphate (non-preferred name), ... (5 entities in total)
• Functional Keywords: formyltransferase, transferase
• Biological source: Anoxybacillus kamchatkensis G10
• Total number of polymer chains: 1
• Total formula weight: 26768.92

Authors

Reimer, J.M.,Harb, I.,Schmeing, T.M. (deposition date: 2018-02-23, release date: 2018-10-17, Last modification date: 2023-10-04)

Primary citation

Reimer, J.M.,Harb, I.,Ovchinnikova, O.G.,Jiang, J.,Whitfield, C.,Schmeing, T.M.
Structural Insight into a Novel Formyltransferase and Evolution to a Nonribosomal Peptide Synthetase Tailoring Domain.
ACS Chem. Biol., 13:3161-3172, 2018

PubMed Abstract: Nonribosomal peptide synthetases (NRPSs) increase the chemical diversity of their products by acquiring tailoring domains. Linear gramicidin synthetase starts with a tailoring formylation (F) domain, which likely originated from a sugar formyltransferase (FT) gene. Here, we present studies on an Anoxybacillus kamchatkensis sugar FT representative of the prehorizontal gene transfer FT. Gene cluster analysis reveals that this FT acts on a UDP-sugar in a novel pathway for synthesis of a 7-formamido derivative of CMP-pseudaminic acid. We recapitulate the pathway up to and including the formylation step in vitro, experimentally demonstrating the role of the FT. We also present X-ray crystal structures of the FT alone and with ligands, which unveil contrasts with other structurally characterized sugar FTs and show close structural similarity with the F domain. The structures reveal insights into the adaptations that were needed to co-opt and evolve a sugar FT into a functional and useful NRPS domain.

PubMed: 30346688
DOI: 10.1021/acschembio.8b00739

Experimental method

X-RAY DIFFRACTION (2.00003052726 Å)