Searching sequence space: Two different approaches to dihydrofolate reductase catalysis

被引：55

作者：

Howell, EE ^{[1
]}

机构：

[1] Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN 37996 USA

来源：

CHEMBIOCHEM | 2005年 / 6卷 / 04期

关键词：

antibiotics; enthalpy; enzyme catalysis; enzyme evolution; protein engineering;

D O I：

10.1002/cbic.200400237

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：

There are numerous examples of proteins that catalyze the some reaction while possessing different structures. This review focuses on two dihydrofolate reductases (DHFRs) that have disparate structures and discusses how the catalytic strategies of these two DHFRs are driven by their respective scaffolds. The two proteins ore E. coli chromosomal DHFR (Ec DHFR) and a type II R-plasmid-encoded DHFR, typified by R67 DHFR. The former has been described as a very well evolved enzyme with an efficiency of 0.15, while the latter has been suggested to be a model for a "primitive" enzyme that has not yet been optimized by evolution. This comparison underlines what is important to catalysis in these two enzymes and concurrently highlights fundamental issues in enzyme catalysis.

引用

页码：591 / 600

页数：10

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