Download MendeleyStructure analysis of peptide deformylases from streptococcus pneumoniae,staphylococcus aureus, thermotoga maritima, and pseudomonas aeruginosa: snapshots of the oxygen sensitivity of peptide deformylase
Kreusch, A., Spraggon, G., Lee, C.C., Klock, H., McMullan, D., Ng, K., Shin, T., Vincent, J., Warner, I., Ericson, C., Lesley, S.A.(2003) J Mol Biol 330: 309-321
- PubMed: 12823970
- DOI: https://doi.org/10.1016/s0022-2836(03)00596-5
- Primary Citation of Related Structures:
1LM4, 1LM6, 1LME, 1N5N - PubMed Abstract:
Peptide deformylase (PDF) has received considerable attention during the last few years as a potential target for a new type of antibiotics. It is an essential enzyme in eubacteria for the removal of the formyl group from the N terminus of the nascent polypeptide chain. We have solved the X-ray structures of four members of this enzyme family, two from the Gram-positive pathogens Streptococcus pneumoniae and Staphylococcus aureus, and two from the Gram-negative bacteria Thermotoga maritima and Pseudomonas aeruginosa. Combined with the known structures from the Escherichia coli enzyme and the recently solved structure of the eukaryotic deformylase from Plasmodium falciparum, a complete picture of the peptide deformylase structure and function relationship is emerging. This understanding could help guide a more rational design of inhibitors. A structure-based comparison between PDFs reveals some conserved differences between type I and type II enzymes. Moreover, our structures provide insights into the known instability of PDF caused by oxidation of the metal-ligating cysteine residue.
Organizational Affiliation:
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA. [email protected]
