Links

Tools

Export citation

Search in Google Scholar

Molecular modeling and functional characterization of a pertinent enzyme in Streptococcus pneumoniae serotype-2: A potential target for the development of novel pneumonia drug

This paper is available in a repository.
This paper is available in a repository.

Full text: Download

Question mark in circle
Preprint: policy unknown
Question mark in circle
Postprint: policy unknown
Question mark in circle
Published version: policy unknown

Abstract

Streptococcus pneumoniae is the causative agent of Pneumonia resulting in a substantial portion of childhood deaths in Bangladesh. Though drugs are in sufficient availability but the emergence of multi-drug resistant varieties of S. pneumoniae has led to the search for novel drug targets. The metabolic pathways of host (Homo sapiens) and pathogen (S. pneumoniae serotype-2) were compared where six biochemical pathways of S. pneumonia, distinct from human pathways, were identified. These comprised of 20 unique enzymes, which being non-homologous proteins in contrast to human host proteins, can be considered as probable drug targets. Among them, the 3D structure of an uncharacterized protein molecule was built in by homology modeling and the binding pockets of protein molecule responsible for specific functions were identified. These structural and functional characterizations of the protein, unique in S. pneumoniae in host condition, made the possibility for the sophisticated rational drug design. Introduction Pneumonia remains a leading cause of mortality in pediatric population of Bangladesh 1 , covering about 52 thousands childhood deaths in the year 2008 2 . Published comparison of incidence between developing and developed countries indicates that 90 to 95% of clinical pneumonia occurs in developing countries 1 . It is defined as the presence of cough or difficulty in breathing, with other clinical symptoms and signs. The pathogens that cause pneumonia are Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, and Gram negative bacteria, such as, Escherichia coli and Klebsiella spp.. Among them, S. pneumoniae serotype-2 is the most prevalent pathogen in Bangladesh 3,4 . It is a Gram positive bacteria frequently colonizing the nasopharynx. Invasive infection can develop in a variety of body compartments including blood, lungs, cerebrospinal fluid and middle ear 5 . Though different drugs are available for the treatment but increasing incidence of multiple-antimicrobial drug resistance among S. pneumoniae isolates is becoming a problem throughout the world 6 . Therefore, the realization to manufacture novel drugs is important.