Molecular modelling of urease accessory interaction proteins of Helicobacter Pylori J 99 and predicting an interruption in interaction by Vigna radiata Defensins

Manivannan Paramasivan,Ganesan Sankaran,Naveenkumar Sethuraman,Sathiamoorthi Thangavelu,Muralitharan Gangatharan,Daniel Selvakumar Devadoss

doi:10.6026/97320630005410

Abstract

Helicobacter pylori is the major causative agent of Gastric carcinoma. Significance of the urease accessory interaction proteins are emphasized in colonization of human gastric mucosa and efficient infection of H. pylori. Here an attempt is made to explore the structure and properties of urease accessory interaction proteins from Helicobacter pylori J 99. The proteins chosen for the study are ureH, ureI, nikR, groL and flgS based on the interaction map available from STRING database. The above mentioned proteins do not have a comprehensive three dimensional structure. Hence the models were generated using PSI-BLAST (Position Specific Iterative-Blast) and MODELLER 9V8. Physicochemical characterization encompasses pI, EC, AI, II and GRAVY. Secondary structure was predicted using PSI-PRED. Functional characterization was done by SOSUI and DISULFIND Servers and refinement of structure was done using Ramachandran plot analysis. RMS-Z values were calculated using Q-MEAN Server and CHIMERA was used for molecular simulation studies. Plant defensins from Vigna radiata are successfully docked to the modeled structures and thus interaction could be possibly prevented. These results will pave way for further selective inhibition of H. pylori colonization and in vivo survival by employing plant defensins from Vigna radiata (VrD1 & VrD2). The work will prove that plant defensins provides anticancer relief too.

Highlights

Helicobacter pylori is a gram negative microaerophilic bacterium causing chronic gastritis, peptic ulcer and gastric carcinoma [1, 2]
The sequences retrieved from STRING database are tabulated in Table 1 and physicochemical parameters, SOSUI server results, Disulphide bond patterns and RMS-Z score values are computed and compiled in Table 2, 3, 4 and 5(see Supplementary material) respectively
The urease accessory interaction proteins are inactive in its apo form [5, 6] and upon conformational change in to holo enzyme, they require an interaction among nine proteins ranging from ureA to flgS

Summary

Background

Helicobacter pylori is a gram negative microaerophilic bacterium causing chronic gastritis, peptic ulcer and gastric carcinoma [1, 2]. Urease is assembled invivo as an inactive apoenzyme and undergoes a maturation process that involves Ni2+ incorporation and lysine carbamylation to produce a fully active holoenzyme This assembly requires the significant involvement of urease accessory proteins and affirmative from the invivo studies using yeast two hybrid analysis [5, 6], coimmunoprecipation assays [6] which reveals a direct interaction between ureG and ureE. In this paper, interacting proteins namely, ureH, ureI, nikR, groL and flgS from Helicobacter pylori J99 which are devoid of a complete structure are chosen for modeling and insilico analysis. In this study an attempt is made to dock the VrD1 and VrD2 (Vigna radiata) defensin proteins and urease interaction proteins of Helicobacter pylori J99. Docking studies: Protein structures of VrD1 and VrD2 plant defensins of Vigna radiata was retrieved from Protein Data Bank with Accession numbers 1T15 and 2GL1. Energy minimization was performed before and after docking using GROMOS96 version of SWISS-PDB Viewer [26]

Discussion

Conclusion:

References: