title: In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase.
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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India.
authors.forename: Pasupuleti Santhosh
authors.initials: PS
authors.lastname: Kumar
authors.affiliation: Department of Zoology, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.
authors.forename: Yellapu Nanda
authors.initials: YN
authors.lastname: Kumar
authors.affiliation: Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India.
authors.forename: Uppu Venkateswara
authors.initials: UV
authors.lastname: Prasad
authors.affiliation: Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India.
authors.forename: Sthanikam
authors.initials: S
authors.lastname: Yeswanth
authors.affiliation: Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India.
authors.forename: Vimjam
authors.initials: V
authors.lastname: Swarupa
authors.affiliation: Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India.
authors.forename: Gopal
authors.initials: G
authors.lastname: Sowjenya
authors.affiliation: Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India.
authors.forename: Katari
authors.initials: K
authors.lastname: Venkatesh
authors.affiliation: Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India.
authors.forename: Lokanathan
authors.initials: L
authors.lastname: Srikanth
authors.affiliation: Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Valasani Koteswara
authors.initials: VK
authors.lastname: Rao
authors.affiliation: Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India.
authors.forename: Potukuchi Venkata Gurunatha Krishna
authors.initials: PV
authors.lastname: Sarma
keywords: Dioxovolerate; homology modeling; molecular operating environment; porphobilinogen synthase