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.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Kreusch A,Spraggon G,Lee CC,Klock H,McMullan D,Ng K,Shin T,Vincent J,Warner I,Ericson C,Lesley SAdoi
10.1016/s0022-2836(03)00596-5keywords:
subject
Has Abstractpub_date
2003-07-04 00:00:00pages
309-21issue
2eissn
0022-2836issn
1089-8638pii
S0022283603005965journal_volume
330pub_type
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