1JWP

Structure of M182T mutant of TEM-1 beta-lactamase

1JWP の概要

• エントリーDOI: 10.2210/pdb1jwp/pdb
• 分子名称: BETA-LACTAMASE TEM, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: protein stability, tem-1, beta-lactamase, antibiotic resistance, evolution, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29006.88

構造登録者

Wang, X.,Minasov, G.,Shoichet, B.K. (登録日: 2001-09-04, 公開日: 2002-06-05, 最終更新日: 2024-10-30)

主引用文献

Wang, X.,Minasov, G.,Shoichet, B.K.
Evolution of an antibiotic resistance enzyme constrained by stability and activity trade-offs.
J.Mol.Biol., 320:85-95, 2002

PubMed Abstract: Pressured by antibiotic use, resistance enzymes have been evolving new activities. Does such evolution have a cost? To investigate this question at the molecular level, clinically isolated mutants of the beta-lactamase TEM-1 were studied. When purified, mutant enzymes had increased activity against cephalosporin antibiotics but lost both thermodynamic stability and kinetic activity against their ancestral targets, penicillins. The X-ray crystallographic structures of three mutant enzymes were determined. These structures suggest that activity gain and stability loss is related to an enlarged active site cavity in the mutant enzymes. In several clinically isolated mutant enzymes, a secondary substitution is observed far from the active site (Met182-->Thr). This substitution had little effect on enzyme activity but restored stability lost by substitutions near the active site. This regained stability conferred an advantage in vivo. This pattern of stability loss and restoration may be common in the evolution of new enzyme activity.

PubMed: 12079336
DOI: 10.1016/S0022-2836(02)00400-X

実験手法

X-RAY DIFFRACTION (1.75 Å)