Crystal structure of type II peptide deformylase from Staphylococcus aureus.
The first crystal structure of Class II peptide deformylase has been determined. The enzyme from Staphylococcus aureus has been overexpressed and purified in Escherichia coli and the structure determined by x-ray crystallography to 1.9 A resolution. The purified iron-enriched form of S. aureus peptide deformylase enzyme retained high activity over many months. In contrast, the iron-enriched form of the E. coli enzyme is very labile. Comparison of the two structures details many differences; however, there is no structural explanation for the dramatic activity differences we observed. The protein structure of the S. aureus enzyme reveals a fold similar, but not identical to, the well characterized E. coli enzyme. The most striking deviation of the S. aureus from the E. coli structure is the unique conformation of the C-terminal amino acids. The distinctive C-terminal helix of the latter is replaced by a strand in S. aureus which wraps around the enzyme, terminating near the active site. Although there are no differences at the amino acid level near the active site metal ion, significant changes are noted in the peptide binding cleft which may play a role in the design of general peptide deformylase inhibitors.
Baldwin
Eric T
ET
Department of Structural Analytical and Medicinal Chemistry, Pharmacia, 301 Henrietta Street, Kalamazoo, MI 49007, USA. eric.t.baldwin@pharmacia.com
Harris
Melissa S
MS
Yem
Anthony W
AW
Wolfe
Cindy L
CL
Vosters
Anne F
AF
Curry
Kimberly A
KA
Murray
Robert W
RW
Bock
Jeffrey H
JH
Marshall
Vincent P
VP
Cialdella
Joyce I
JI
Merchant
Mahesh H
MH
Choi
Gil
G
Deibel
Martin R
MR
D000581:Amidohydrolases; D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D003460:Crystallization; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D013211:Staphylococcus aureus / Q000201:enzymology*
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase