full issue - Association of Biotechnology and Pharmacy

Current Trends in Biotechnology and Pharmacy
Vol. 5 (3) 1318 -1324 July 2011, ISSN 0973-8916 (Print), 2230-7303 (Online)
Docking and Molecular Modelling of the Target - Penicillin
Binding Protein -1A of Haemophilus influenzae
B.N. Ramya Jyothi, K. Siva Prasad and S. Krupanidhi*
Centre for Bioinformatics, Department of Zoology, Sri Venkateswara University, Tirupati – 517 502. A.P. India.
*Department of Biosciences, Sri Satya Sai Institute of Higher Learning, Prasanthi Nilayam - 515 134, India
*For Correspondence - krupanidhi_srirama@rediffmail.com
1318
Abstract
Penicillin binding protein-1A (PBP-1A;
IPR011816) plays a pivotal role in the biogenesis
of cell-wall and biosynthesis of peptidoglycan
in bacteria. It is considered to be a novel target
for pneumonia. The present study is to deduce
the structure of the PBP-1A using ICM Molsoft
and to validate the same with Ramachandran
plot. These bioinformatics tools have been used
to identify a lead molecule against PBP-1A of
Haemophilus influenza. The proposed model
structure is further explored for in silico docking
studies with suitable inhibitors. The docking
scores indicated that the ampicillin could be a
better inhibitor among the seven antibiotics
chosen in the present investigation.
Key words: Haemophilus influenzae strain 86-
028NP, PBP protein, ICM Molsoft, Argus lab
4.0.1, Gold.
Introduction
Pneumonia is an inflammation of lungs,
usually caused by a pathogen. Three common
causative groups of pathogens that cause
pneumonia are bacteria, viruses and fungi (1).
The people at risk are older than 65 or younger
than 2 years of age, or those with impaired
immunity. Some of the gram-negative bacteria
that cause pneumonia include Haemophilus
influenzae (HI), Klebsiella pneumoniae,
Escherichia coli, Pseudomonas aeruginosa and
Moraxella catarrhalis.
HI is a non-motile gram-negative
bacterium belonging to the family
Pasteurellaceae. Pneumonia caused by HI seems
to occur exclusively among humans. HI was first
isolated by Pfeiffer during the influenza
pandemic of 1890. This pathogen is present in
the nasopharynx of approximately 75 percent of
healthy children and adults. It is rarely
encountered in the oral cavity and has not been
detected in any other animal species (2). HI was
the first pathogenic organism to have its entire
genome sequenced during the year 1995 (3).
Bacterial cell wall and PBPs are the targets
for drugs of selective toxicity because the related
metabolic pathways and enzymes are unique to
prokaryotes (4). Whereas, mitogen-activated
protein kinase and trypanothione reductase are
considered as targets in a eukaryotic protozoan
parasite viz., Leishmania infantum (5, 6).
However, in bacterial system, PBPs have been
shown to catalyse a variety of reactions involved
in the process of synthesizing cross-linked
peptidoglycan from lipid intermediates and
mediate the removal of D-alanine from the
precursor of peptidoglycan (7). PBP-1A in HI
strain 86-028np is coded by mrcA gene. This
possesses two domains viz., penicillin-insensitive
transglycosylase EC=2.4.2.- and penicillin-
Docking of the penicillin binding protein of Haemophilus influenzae