The protein peptide deformylase of Escherichia coli consists of a single domain of 168 amino acid residues, and it is a zinc containing protein. Peptide deformylase (PDF) represents a new subfamily of metalloproteases with interesting physical and catalytic properties. The protein contains three major a-helices, three b-sheet regions, and a potentially critical 3-10 helix. Recently, it has been found that PDF may act as drug target. We have done molecular dynamics simulation of zinc containing peptide deformylase of E. coli. The local and global motional properties like Root Mean Square Deviation (RMSD), radius of gyration (Rg), etc. are computed. RMSD of the secondary structure elements gives light towards the structural and functional properties due to local motion of the protein. Overall studies show that the protein is not much flexible and it has no other stable conformer. The functional ability of deformylation and restricted motional properties make this protein a good target for drug molecules.

Peptide deformylase (PDF) is essential for the initiation of translation in eubacteria but not in eukaryotes. The N-formylmethionine of the nascent protein in bacteria is removed by the sequential action of PDF and a methionine amino peptidase in order to afford the mature protein (Meinnel and Blanquet, 1993; and Adams et al., 1966). This formylation-deformylation cycle is essential for the bacterial growth and is conserved among all the studied bacterial species. PDF (EC 3.5.1.27) is essential for the normal growth of eubacterium, but not for mammalians. The specific bacterial requirement for PDF in protein synthesis provides a rational basis for selectivity, making it an attractive drug discovery target. Its activity is strongly dependent on the bound metal ion.

PDF has high specificity towards N-formylated substrates and it is responsible for the deformylation of N-terminal formyl group of nascent protein. This metalloprotein contains HEXXH motif, which is a characteristic of zinc containing metalloprotein. Mutagenesis studies have been done for identifying the residues that serve as ligand for the metal. It was observed by Meinnel et al. (1995) that Cys-90 serves as ligand. It is found a tetrahedral metal ion is found in the three-dimensional structure, with side chains of Cys-90, His-132, and His-136 from the protein, and a bound water molecule as its ligands.

Biotechnology Journal, Peptide Deformylase, Molecular Dynamics Simulation, Vacuum Environment, Aqueous Environment, Peptide Deformylase, Root Mean Square Deviation, RMSD, Formylation-deformylation Cycle, Crystal Structure, Crystal Structure, Cartesian Equations, Linux Environment, N-Formylmethionyl.