 |
PDBsum entry 2zc5
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Biosynthetic protein
|
PDB id
|
|
|
|
2zc5
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structures of biapenem and tebipenem complexed with penicillin-Binding proteins 2x and 1a from streptococcus pneumoniae.
|
|
|
Authors
|
|
M.Yamada,
T.Watanabe,
N.Baba,
Y.Takeuchi,
F.Ohsawa,
S.Gomi.
|
|
|
Ref.
|
|
Antimicrob Agents Chemother, 2008,
52,
2053-2060.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Biapenem is a parenteral carbapenem antibiotic that exhibits wide-ranging
antibacterial activity, remarkable chemical stability, and extensive stability
against human renal dehydropeptidase-I. Tebipenem is the active form of
tebipenem pivoxil, a novel oral carbapenem antibiotic that has a high level of
bioavailability in humans, in addition to the above-mentioned features.
beta-lactam antibiotics, including carbapenems, target penicillin-binding
proteins (PBPs), which are membrane-associated enzymes that play essential roles
in peptidoglycan biosynthesis. To envisage the binding of carbapenems to PBPs,
we determined the crystal structures of the trypsin-digested forms of both PBP
2X and PBP 1A from Streptococcus pneumoniae strain R6, each complexed with
biapenem or tebipenem. The structures of the complexes revealed that the
carbapenem C-2 side chains form hydrophobic interactions with Trp374 and Thr526
of PBP 2X and with Trp411 and Thr543 of PBP 1A. The Trp and Thr residues are
conserved in PBP 2B. These results suggest that interactions between the C-2
side chains of carbapenems and the conserved Trp and Thr residues in PBPs play
important roles in the binding of carbapenems to PBPs.
|
|
|
|
|
|
|
