Crystal structures and kinetic analyses of N-acetylmannosamine-6-phosphate 2-epimerases from Fusobacterium nucleatum and Vibrio cholerae

Manjunath, Lavanyaa and Guntupalli, Sai Rohit (2018) Crystal structures and kinetic analyses of N-acetylmannosamine-6-phosphate 2-epimerases from Fusobacterium nucleatum and Vibrio cholerae. Acta Cryst, 74. pp. 431-440. ISSN 2053-230X

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Abstract

Sialic acids are nine-carbon sugars that are found abundantly on the cell surfaces of mammals as glycoprotein or glycolipid complexes. Several Gram-negative and Gram-positive bacteria have the ability to scavenge and catabolize sialic acids to use as a carbon source. This gives them an advantage in colonizing sialic acid-rich environments. The genes of the sialic acid catabolic pathway are generally present as the operon nanAKE. The third gene in the operon encodes the enzyme N- acetylmannosamine-6-phosphate 2-epimerase (NanE), which catalyzes the conversion of N-acetylmannosamine 6- hosphate to N-acetylglucosamine 6-phosphate, thus committing it to enter glycolysis. The NanE enzyme belongs to the isomerase class of enzymes possessing the triose phosphate isomerase (TIM) barrel fold. Here, comparative structural and functional characterizations of the NanE epimerases from two pathogenic Gram-negative bacteria, Fusobacterium nucleatum (Fn) and Vibrio cholerae (Vc), have been carried out. Structures of NanE from Vc (VcNanE) with and without ligand bound have been determined to 1.7 and 2.7 A ˚ resolution, respectively. The structure of NanE from Fn (FnNanE) has been determined to 2.2 A ˚ resolution. The enzymes show kinetic parameters that are consistent with those of Clostridium perfringens NanE. These studies allowed an evaluation of whether NanE may be a good drug target against these pathogenic bacteria.

Item Type: Article
Uncontrolled Keywords: Sialic acid catabolism; N-acetylmannosamine-6-phosphate 2-epimerase; Fusobacterium nucleatum; Vibrio cholerae
Subjects: Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 07 Feb 2019 08:57
Last Modified: 07 Feb 2019 08:57
URI: http://eprints.manipal.edu/id/eprint/153200

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