Structure analysis of peptide deformylases from Streptococcus pneumoniae, Staphylococcus aureus, Thermotoga maritima and Pseudomonas aeruginosa: snapshots of the oxygen sensitivity of peptide deformylase.
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.
Kreusch
Andreas
A
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA. kreusch@gnf.org
Spraggon
Glen
G
Lee
Chris C
CC
Klock
Heath
H
McMullan
Daniel
D
Ng
Ken
K
Shin
Tanya
T
Vincent
Juli
J
Warner
Ian
I
Ericson
Christer
C
Lesley
Scott A
SA
D000581:Amidohydrolases; D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D001665:Binding Sites; D018360:Crystallography, X-Ray; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010084:Oxidation-Reduction; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics; D055672:Static Electricity; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000235:genetics; D020124:Thermotoga maritima / Q000201:enzymology* / Q000235:genetics
D011994:Recombinant Proteins; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase