Characterization of peptide deformylase homologues from Staphylococcus epidermidis.
The emergence of multi-drug-resistant strains of Staphylococcus epidermidis emphasizes the need to develop new antibiotics. The unique and essential role of the peptide deformylase (PDF) in catalysing the removal of the N-terminal formyl group from newly synthesized polypeptides in eubacteria makes it an attractive antibacterial drug target. In the present study, both deformylase homologues from S. epidermidis (SePDF-1 and SePDF-2) were cloned and expressed, and their enzymic activities were characterized. Co(2+)-substituted SePDF-1 exhibited much higher enzymic activity (k(cat)/K(m) 6.3 × 10(4) M(-1) s(-1)) than those of Ni(2+)- and Zn(2+)-substituted SePDF-1, and SePDF-1 showed much weaker binding ability towards Ni(2+) than towards Co(2+) and Zn(2+), which is different from PDF in Staphylococcus aureus (SaPDF), although they share 80 % amino-acid sequence identity. The determined crystal structure of SePDF-1 was similar to that of (SaPDF), except for differences in the metal-binding sites. The other deformylase homologue, SePDF-2, was shown to have no peptide deformylase activity; the function of SePDF-2 needs to be further investigated.
Lin
Penghui
P
Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Hu
Tiancen
T
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Hu
Jian
J
Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Yu
Wenqi
W
Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Han
Cong
C
Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Zhang
Jian
J
Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education of China, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China.
Qin
Guangrong
G
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Yu
Kunqian
K
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Götz
Friedrich
F
Microbial Genetics, University of Tübingen, Auf der Morgenstelle 28, D-72076 Tübingen, Germany.
Shen
Xu
X
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Jiang
Hualiang
H
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Qu
Di
D
Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D003001:Cloning, Molecular; D003035:Cobalt / Q000378:metabolism; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009532:Nickel / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013212:Staphylococcus epidermidis / Q000201:enzymology* / Q000235:genetics; D015032:Zinc / Q000378:metabolism
D001426:Bacterial Proteins; D003035:Cobalt; D009532:Nickel; D000581:Amidohydrolases; C084507:peptide deformylase; D015032:Zinc