Crystal structure of the membrane-bound bifunctional transglycosylase PBP1b from Escherichia coli.
Drug-resistant bacteria have caused serious medical problems in recent years, and the need for new antibacterial agents is undisputed. Transglycosylase, a multidomain membrane protein essential for cell wall synthesis, is an excellent target for the development of new antibiotics. Here, we determined the X-ray crystal structure of the bifunctional transglycosylase penicillin-binding protein 1b (PBP1b) from Escherichia coli in complex with its inhibitor moenomycin to 2.16-A resolution. In addition to the transglycosylase and transpeptidase domains, our structure provides a complete visualization of this important antibacterial target, and reveals a domain for protein-protein interaction and a transmembrane helix domain essential for substrate binding, enzymatic activity, and membrane orientation.
Sung
Ming-Ta
MT
Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Taipei 115, Taiwan.
Lai
Yen-Ting
YT
Huang
Chia-Ying
CY
Chou
Lien-Yang
LY
Shih
Hao-Wei
HW
Cheng
Wei-Chieh
WC
Wong
Chi-Huey
CH
Ma
Che
C
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry; D046915:Penicillin-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D046928:Peptidoglycan Glycosyltransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011487:Protein Conformation; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase / Q000037:antagonists & inhibitors* / Q000737:chemistry*
D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D009844:Oligosaccharides; D046915:Penicillin-Binding Proteins; D046928:Peptidoglycan Glycosyltransferase; C478681:penicillin-binding protein 1B, E coli; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; C419802:moenomycin