7N7B

crystal structure of the N-formyltrasferase HCAN_0200 from Helicobacter canadensis on complex with folinic acid and dTDP-3-aminofucose

Summary for 7N7B

• Entry DOI: 10.2210/pdb7n7b/pdb
• Related: 7n7a
• Descriptor: Formyl_trans_N domain-containing protein, N-{[4-({[(6R)-2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]carbonyl}-L-glutamic acid, (3R,4S,5R,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl][hydroxy-[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphoryl] hydrogen phosphate, ... (6 entities in total)
• Functional Keywords: folinic acid, formyltransferase, aminofucose, transferase
• Biological source: Helicobacter canadensis MIT 98-5491
• Total number of polymer chains: 2
• Total formula weight: 68678.46

Authors

Heisdorf, C.J.,Thoden, J.B.,Holden, H.M. (deposition date: 2021-06-10, release date: 2021-06-23, Last modification date: 2023-10-18)

Primary citation

Heisdorf, C.J.,Griffiths, W.A.,Thoden, J.B.,Holden, H.M.
Investigation of the enzymes required for the biosynthesis of an unusual formylated sugar in the emerging human pathogen Helicobacter canadensis.
Protein Sci., 30:2144-2160, 2021

PubMed Abstract: It is now well established that the Gram-negative bacterium, Helicobacter pylori, causes gastritis in humans. In recent years, it has become apparent that the so-called non-pylori Helicobacters, normally infecting pigs, cats, and dogs, may also be involved in human pathology via zoonotic transmission. Indeed, more than 30 species of non-pylori Helicobacters have been identified thus far. One such organism is Helicobacter canadensis, an emerging pathogen whose genome sequence was published in 2009. Given our long-standing interest in the biosynthesis of N-formylated sugars found in the O-antigens of some Gram-negative bacteria, we were curious as to whether H. canadensis produces such unusual carbohydrates. Here, we demonstrate using both biochemical and structural techniques that the proteins encoded by the HCAN_0198, HCAN_0204, and HCAN_0200 genes in H. canadensis, correspond to a 3,4-ketoisomerase, a pyridoxal 5'-phosphate aminotransferase, and an N-formyltransferase, respectively. For this investigation, five high-resolution X-ray structures were determined and the kinetic parameters for the isomerase and the N-formyltransferase were measured. Based on these data, we suggest that the unusual sugar, 3-formamido-3,6-dideoxy-d-glucose, will most likely be found in the O-antigen of H. canadensis. Whether N-formylated sugars found in the O-antigen contribute to virulence is presently unclear, but it is intriguing that they have been observed in such pathogens as Francisella tularensis, Mycobacterium tuberculosis, and Brucella melitensis.

PubMed: 34379357
DOI: 10.1002/pro.4169

Experimental method

X-RAY DIFFRACTION (2 Å)