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