Crystal structure of a GDP-6-OMe-4-keto-L-xylo-heptose reductase from Campylobacter jejuni

• Published in: Proteins, structure, function, and bioinformatics Vol. 89; no. 8; pp. 1030 - 1038
• Main Authors: Kim, Jun-Hong, Hofmann, Andreas, Kim, Jeong-Sun
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.08.2021
• Subjects: Biosynthesis; Campylobacter; Campylobacter jejuni; Carbohydrates; Crystal structure; Domains; Enzymes; Epimerase; Gastroenteritis; Heptose; Pathogens; Reductase; Reductases; Residues; Substrate specificity; Substrates; Tyrosine; Virulence; heptose; MlghC; carbohydrate; C4 reductase
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.26080

Carbohydrates play a major role in infection strategies of various enteric pathogens. In Campylobacter jejuni, the most common cause of gastroenteritis, uniquely modified heptoses found in surface carbohydrates are synthesized by specific pathways. Owing to the importance of such pathways for the infectious potential of pathogens and/or their virulence, these biosynthesis pathways present potential targets for therapeutic intervention. Here, we determined the crystal structure of GDP-6-OMe-4-keto-L-xylo-heptose reductase (MlghC), an enzyme within the L-gluco-heptose synthesis pathway of C. jejuni strain NCTC 11168. This enzyme lacks the canonical tyrosine residue of the conserved catalytic Ser-Lys-Tyr triad commonly found among functionally related reductases. Despite adopting the overall two-domain fold shared with other short-chain dehydrogenase/reductase family members, subtle structural differences in the interface between the cofactor- and substrate-binding domains explain the absence of epimerase activity and different substrate specificity of this reductase. Modeling of the product-bound complex based on the crystal structure presented here suggests that a tyrosine residue unique to MlghC replaces the missing canonical residue of the catalytic triad.