Investigating protein structural plasticity by surveying the consequence of an amino acid deletion from TEM-1 β-lactamase

被引:32
作者
Simm, Alan M. [1 ]
Baldwin, Amy J. [1 ]
Busse, Kathy [1 ]
Jones, D. Dafydd [1 ]
机构
[1] Cardiff Univ, Sch Biosci, Cardiff CF10 3US, Wales
基金
英国生物技术与生命科学研究理事会;
关键词
protein plasticity; directed evolution; deletion mutations; indels; antibiotic resistance;
D O I
10.1016/j.febslet.2007.07.018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
While the deletion of an amino acid is a common mutation observed in nature, it is generally thought to be disruptive to protein structure. Using a directed evolution approach, we find that the enzyme TEM-1 beta-lactamase was broadly tolerant to the deletion mutations sampled. Circa 73% of the variants analysed retained activity towards ampicillin, with deletion mutations observed in helices and strands as well as regions important for structure and function. Several deletion variants had enhanced activity towards ceftazidime compared to the wild-type TEM-1 demonstrating that removal of an amino acid can have a beneficial outcome. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:3904 / 3908
页数:5
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