Molecular and Structural Characterization of GMP Reductase of Streptococcus pneumonia - A Potential Drug Target for Pneumonia

Rajasekhar Chikati

Rajasekhar Chikati Department of Biochemistry, Yogi Vemana University, Kadapa, Andhra Pradesh – 516005

Abstract

Streptococcus pneumoniae remains a major pathogen responsible for high morbidity and mortality in both the developed and developing countries. S. pneumoniae is estimated to kill annually close to one million children less than five years of age worldwide. Today antibiotic resistance in S. pneumoniae is common and increasing. Guanosine monophosphate reductase (GMPR) catalyzes the irreversible and NADPH- dependent reductive deamination of Guanosine Mono Phosphate (GMP) to Inosine Mono Phosphate (IMP) and plays a critical role in re-utilization of free intracellular bases and purine nucleosides. In this paper we had built the 3D structure of GMP reductase of Streptococcus pneumonia-R6 by comparing the crystal structure of human guanosine monophosphate reductase 2 (hGMPr2, 2A7R). 3D Structure was built in modeler 9v8 by using information of alignment file developed in ClustalW 1.8.3. Developed GMP reductase S. pneumonia-R6 model was submitted to PROCHECK and WHATIF programs for validation of the stereochemical quality and structure analysis. The Z-score was determined by ProSA web analysis. The developed model was deposited in PMDB and was accepted with <3% stereochemical failures. The present study would provide valuable insight information to search and rational drug design of a new generation of wide spectrum pneumonia drugs through a good understanding of structural characterization of GMP reductase.

Keywords: Streptococcus pneumonia, GMP reductase, Homology modeling, Modeller 9v8, Potential drug targets for Pneumonia

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