6OW7
X-ray Structure of Polypeptide Deformylase with a Piperazic Acid
Summary for 6OW7
| Entry DOI | 10.2210/pdb6ow7/pdb |
| Descriptor | Peptide deformylase, NICKEL (II) ION, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | inhibitor, complex, metal protein, enzyme, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Streptococcus pneumoniae |
| Total number of polymer chains | 2 |
| Total formula weight | 46296.17 |
| Authors | Campobasso, N.,Spletstoser, J.,Ward, P. (deposition date: 2019-05-09, release date: 2019-06-26, Last modification date: 2024-03-13) |
| Primary citation | Spletstoser, J.T.,Dreabit, J.,Knox, A.N.,Benowitz, A.,Campobasso, N.,Ward, P.,Cui, G.,Lewandowski, T.,McCloskey, L.,Aubart, K.M. Discovery of piperazic acid peptide deformylase inhibitors with in vivo activity for respiratory tract and skin infections. Bioorg.Med.Chem.Lett., 29:2410-2414, 2019 Cited by PubMed Abstract: The discovery of a novel series of peptide deformylase inhibitors incorporating a piperazic acid amino acid found in nature is described. These compounds demonstrated potent in vitro enzymatic potency and antimicrobial activity. Crystal structure analysis revealed the piperazic acid optimized a key contact with the PDF protein that accounted for the increased enzymatic potency of these compounds. We describe lead optimization of the P3' region of the series that resulted in a compound with good potency against three target organisms. One molecule showed in vivo efficacy in a rat respiratory infection model but ultimately did not meet candidate progression criteria. PubMed: 31160176DOI: 10.1016/j.bmcl.2019.05.028 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.45 Å) |
Structure validation
Download full validation report
