Crystal structure of the Escherichia coli peptide deformylase.
Protein synthesis in bacteria involves the formylation and deformylation of the N-terminal methionine. As eukaryotic organisms differ in their protein biosynthetic mechanisms, peptide deformylase, the bacterial enzyme responsible for deformylation, represents a potential target for antibiotic studies. Here we report the crystallization and 2.9 A X-ray structure solution of the zinc containing Escherichia coli peptide deformylase. While the primary sequence, tertiary structure, and use of coordinated cysteine suggest that E. coli deformylase belongs to a new subfamily of metalloproteases, the environment around the metal appears to have strong geometric similarity to the active sites of the thermolysin family. This suggests a possible similarity in their hydrolytic mechanisms. Another important issue is the origin of the enzyme's specificity for N-formylated over N-acetylated substrates. Based on the structure, the specificity appears to result from hydrogen-bonding interactions which orient the substrate for cleavage, and steric factors which physically limit the size of the N-terminal carbonyl group.
Chan
M K
MK
Department of Biochemistry, Ohio State University, Columbus 43210, USA. chan@chemistry.ohio-state.edu
Gong
W
W
Rajagopalan
P T
PT
Hao
B
B
Tsai
C M
CM
Pei
D
D
D000581:Amidohydrolases; D000626:Aminopeptidases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy; D008667:Metalloproteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D013820:Thermolysin / Q000737:chemistry; D015032:Zinc / Q000378:metabolism
D008667:Metalloproteins; D000626:Aminopeptidases; D013820:Thermolysin; D000581:Amidohydrolases; C084507:peptide deformylase; D015032:Zinc