Protein promiscuity and its implications for biotechnology

被引:398
作者
Nobeli, Irene [1 ]
Favia, Angelo D. [2 ]
Thornton, Janet M. [2 ]
机构
[1] Univ London, Sch Crystallog, Inst Struct & Mol Biol, London WC1E 7HX, England
[2] European Bioinformat Inst, EMBL Outstn Hinxton, Cambridge CB10 1SD, England
关键词
CONFORMATIONAL HETEROGENEITY; CATALYTIC PROMISCUITY; MOLECULAR COMPLEXITY; DIVERGENT EVOLUTION; ENOLASE SUPERFAMILY; CARBONIC-ANHYDRASE; ENZYME PROMISCUITY; DIRECTED EVOLUTION; CROSS-REACTIVITY; PYRUVATE-KINASE;
D O I
10.1038/nbt1519
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Molecular recognition between proteins and their interacting partners underlies the biochemistry of living organisms. Specificity in this recognition is thought to be essential, whereas promiscuity is often associated with unwanted side effects, poor catalytic properties and errors in biological function. Recent experimental evidence suggests that promiscuity, not only in interactions but also in the actual function of proteins, is not as rare as was previously thought. This has implications not only for our fundamental understanding of molecular recognition and how protein function has evolved over time but also in the realm of biotechnology. Understanding protein promiscuity is becoming increasingly important not only to optimize protein engineering applications in areas as diverse as synthetic biology and metagenomics but also to lower attrition rates in drug discovery programs, identify drug interaction surfaces less susceptible to escape mutations and potentiate the power of polypharmacology.
引用
收藏
页码:157 / 167
页数:11
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