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Kumar PS, Kumar YN, Prasad UV, et al. In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase. J Pharm Bioallied Sci. 2014;6(3):158-66doi: 10.4103/0975-7406.135246.
Kumar, P. S., Kumar, Y. N., Prasad, U. V., Yeswanth, S., Swarupa, V., Sowjenya, G., Venkatesh, K., Srikanth, L., Rao, V. K., & Sarma, P. V. (2014). In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase. Journal of pharmacy & bioallied sciences, 6(3), 158-66. https://doi.org/10.4103/0975-7406.135246
Kumar, Pasupuleti Santhosh, et al. "In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase." Journal of pharmacy & bioallied sciences vol. 6,3 (2014): 158-66. doi: https://doi.org/10.4103/0975-7406.135246
Kumar PS, Kumar YN, Prasad UV, Yeswanth S, Swarupa V, Sowjenya G, Venkatesh K, Srikanth L, Rao VK, Sarma PV. In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase. J Pharm Bioallied Sci. 2014 Jul;6(3):158-66. doi: 10.4103/0975-7406.135246. PMID: 25035635; PMCID: PMC4097929.
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J Pharm Bioallied Sci. 2014 Jul;6(3):158-66. doi: 10.4103/0975-7406.135246.

In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase.

Journal of pharmacy & bioallied sciences

Pasupuleti Santhosh Kumar, Yellapu Nanda Kumar, Uppu Venkateswara Prasad, Sthanikam Yeswanth, Vimjam Swarupa, Gopal Sowjenya, Katari Venkatesh, Lokanathan Srikanth, Valasani Koteswara Rao, Potukuchi Venkata Gurunatha Krishna Sarma

Affiliations

  1. Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India.
  2. Department of Zoology, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.
  3. Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS 66047, USA.

PMID: 25035635 PMCID: PMC4097929 DOI: 10.4103/0975-7406.135246

Abstract

BACKGROUND: The emergence of multidrug-resistant strains of Staphylococcus aureus, there is an urgent need for the development of new antimicrobials which are narrow and pathogen specific.

AIM: In this context, the present study is aimed to have a control on the staphylococcal infections by targeting the unique and essential enzyme; porphobilinogen synthase (PBGS) catalyzes the condensation of two molecules of δ-aminolevulinic acid, an essential step in the tetrapyrrole biosynthesis. Hence developing therapeutics targeting PBGS will be the promising choice to control and manage the staphylococcal infections. 4,5-dioxovalerate (DV) is known to inhibit PBGS.

MATERIALS AND METHODS: In view of this, in this study, novel dioxovalerate derivatives (DVDs) molecules were designed so as to inhibit PBGS, a potential target of S. aureus and their inhibitory activity was predicted using molecular docking studies by molecular operating environment. The 3D model of PBGS was constructed using Chlorobium vibrioform (Protein Data Bank 1W1Z) as a template by homology modeling method.

RESULTS: The built structure was close to the crystal structure with Z score - 8.97. Molecular docking of DVDs into the S. aureus PBGS active site revealed that they are showing strong interaction forming H-bonds with the active sites of K248 and R217. The ligand-receptor complex of DVD13 showed a best docking score of - 14.4555 kcal/mol among DV and all its analogs while the substrate showed docking score of - 13.0392 kcal/mol showing interactions with S199, K217 indicating that DVD13 can influence structural variations on the enzyme and thereby inhibiting the enzyme.

CONCLUSION: The substrate analog DVD13 is showing significant interactions with active site of PBGS and it may be used as a potent inhibitor to control S. aureus infections.

Keywords: Dioxovolerate; homology modeling; molecular operating environment; porphobilinogen synthase

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