Structural and functional characterization of the Helicobacter pylori cytidine 5'-monophosphate-pseudaminic acid synthase PseF: molecular insight into substrate recognition and catalysis mechanism

• Main Author: Wahid SUH
• Format: Article
• Language: English
• Published: Dove Medical Press 2017-10-01
• Series: Advances and Applications in Bioinformatics and Chemistry
• Subjects: H. pylori; motility; glycosylation; homology modeling; pseudaminic acid
• Online Access: https://www.dovepress.com/structural-and-functional-characterization-of-the-helicobacter-pylori--peer-reviewed-article-AABC

Syeda Umme Habiba Wahid Department of Microbiology, University of Chittagong, Chittagong, Bangladesh Abstract: The bacterium Helicobacter pylori is a human gastric pathogen that can cause a wide range of diseases, including chronic gastritis, peptic ulcer and gastric carcinoma. It is classified as a definitive (class I) human carcinogen by the International Agency for Research on Cancer. Flagella-mediated motility is essential for H. pylori to initiate colonization and for the development of infection in human beings. Glycosylation of the H. pylori flagellum with pseudaminic acid (Pse; 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-l-manno-nonulosonic acid) is essential for flagella assembly and function. The sixth step in the Pse biosynthesis pathway, activation of Pse by addition of a cytidine 5′-monophosphate (CMP) to generate CMP-Pse, is catalyzed by a metal-dependent enzyme pseudaminic acid biosynthesis protein F (PseF) using cytidine 5′-triphosphate (CTP) as a cofactor. No crystal–structural information for PseF is available. This study describes the first three-dimensional model of H. pylori PseF obtained using biocomputational tools. PseF harbors an α/β-type hydrolase fold with a β-hairpin (HP) dimerization domain. Comparison of PseF with other structural homologs allowed identification of crucial residues for substrate recognition and the catalytic mechanism. This structural information would pave the way to design novel therapeutics to combat bacterial infection. Keywords: H. pylori, motility, glycosylation, homology modeling, pseudaminic acid