Structural Identification of Formate Tetrahydrofolate Synthetase from Neisseria meningitidis

Abstract

Neisseria meningitidis, a gram-negative diplococcus, is a life-threatening pathogen that is responsible for causing meningitis and severe sepsis in humans. Over 2.5 million cases of N. meningitidis are reported yearly, with an approximately 10% mortality rate. Structural bioinformatics has been utilized in this research to predict the three-dimensional model of Formate tetrahydrofolate synthetase (FTHFS) of N. meningitidis. The FTHFS of N. meningitidis serogroup B (strain MC58) is a gene product of NMB1839 and is known to play a role in the one-carbon metabolism and transfer one-carbon-containing units to a variety of biosynthetic pathways. The enzyme FTHFS has an alpha/ beta fold and is mainly composed of three domains, in which one is comparatively larger than the other two. The crystal structure of FTHFS from Morella thermoacetica (PDB ID; 1FP7) was used as a template to predict the homology model of N. meningitidis FTFHS. The structural comparison of both enzymes has suggested that the amino acid residues interacting with the active site and potassium moiety were well conserved. This high conservation among crucial residues showed the shared catalytic mechanism by both enzymes. This study provided additional data for research on novel anti-meningitis drug target.