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Specificity of trypsin and chymotrypsin: Loop-motion-controlled dynamic correlation as a determinant
Ma, WZ ; Tang, C ; Lai, LH
刊名biophysical journal
2005
关键词ACTIVE-SITE FLEXIBILITY ALPHA-LYTIC PROTEASE SUBSTRATE-SPECIFICITY MOLECULAR-DYNAMICS ENZYME CATALYSIS VIBRATIONAL DYNAMICS RESIDUE POTENTIALS CONVERTING TRYPSIN SERINE PROTEASES TRANSITION-STATE
DOI10.1529/biophysj.104.057158
英文摘要Trypsin and chymotrypsin are both serine proteases with high sequence and structural similarities, but with different substrate specificity. Previous experiments have demonstrated the critical role of the two loops outside the binding pocket in controlling the specificity of the two enzymes. To understand the mechanism of such a control of specificity by distant loops, we have used the Gaussian network model to study the dynamic properties of trypsin and chymotrypsin and the roles played by the two loops. A clustering method was introduced to analyze the correlated motions of residues. We have found that trypsin and chymotrypsin have distinct dynamic signatures in the two loop regions, which are in turn highly correlated with motions of certain residues in the binding pockets. Interestingly, replacing the two loops of trypsin with those of chymotrypsin changes the motion style of trypsin to chymotrypsin- like, whereas the same experimental replacement was shown necessary to make trypsin have chymotrypsin's enzyme specificity and activity. These results suggest that the cooperative motions of the two loops and the substrate- binding sites contribute to the activity and substrate specificity of trypsin and chymotrypsin.; Biophysics; SCI(E); PubMed; 33; ARTICLE; 2; 1183-1193; 89
语种英语
内容类型期刊论文
源URL[http://ir.pku.edu.cn/handle/20.500.11897/199712]  
专题化学与分子工程学院
推荐引用方式
GB/T 7714
Ma, WZ,Tang, C,Lai, LH. Specificity of trypsin and chymotrypsin: Loop-motion-controlled dynamic correlation as a determinant[J]. biophysical journal,2005.
APA Ma, WZ,Tang, C,&Lai, LH.(2005).Specificity of trypsin and chymotrypsin: Loop-motion-controlled dynamic correlation as a determinant.biophysical journal.
MLA Ma, WZ,et al."Specificity of trypsin and chymotrypsin: Loop-motion-controlled dynamic correlation as a determinant".biophysical journal (2005).
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