| Structural highlights
6ow7 is a 2 chain structure with sequence from "diplococcus_pneumoniae"_(klein_1884)_weichselbaum_1886 "diplococcus pneumoniae" (klein 1884) weichselbaum 1886. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Gene: | defB, def, def_1, def_2, def_3, A5N45_09745, ERS019420_01538, ERS019688_00954, ERS020178_05158, ERS020534_01685, ERS020726_00048, ERS021057_00383, ERS021733_04069, ERS050646_01998, ERS367886_01588, ERS409327_03241, ERS409593_03947, KK0981_34260, NCTC12140_00964 ("Diplococcus pneumoniae" (Klein 1884) Weichselbaum 1886) |
| Activity: | Peptide deformylase, with EC number 3.5.1.88 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[Q939R9_STREE] Removes the formyl group from the N-terminal Met of newly synthesized proteins. Requires at least a dipeptide for an efficient rate of reaction. N-terminal L-methionine is a prerequisite for activity but the enzyme has broad specificity at other positions (By similarity).[HAMAP-Rule:MF_00163]
Publication Abstract from PubMed
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.
Discovery of piperazic acid peptide deformylase inhibitors with in vivo activity for respiratory tract and skin infections.,Spletstoser JT, Dreabit J, Knox AN, Benowitz A, Campobasso N, Ward P, Cui G, Lewandowski T, McCloskey L, Aubart KM Bioorg Med Chem Lett. 2019 May 16. pii: S0960-894X(19)30325-7. doi:, 10.1016/j.bmcl.2019.05.028. PMID:31160176[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Spletstoser JT, Dreabit J, Knox AN, Benowitz A, Campobasso N, Ward P, Cui G, Lewandowski T, McCloskey L, Aubart KM. Discovery of piperazic acid peptide deformylase inhibitors with in vivo activity for respiratory tract and skin infections. Bioorg Med Chem Lett. 2019 May 16. pii: S0960-894X(19)30325-7. doi:, 10.1016/j.bmcl.2019.05.028. PMID:31160176 doi:http://dx.doi.org/10.1016/j.bmcl.2019.05.028
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