dorsal/arxiv
View SchemaSpecificity of Trypsin and Chymotrypsin: Loop Motion Controlled Dynamic Correlation as a Determinant
| Authors | Wenzhe Ma, Chao Tang, Luhua Lai |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0505037 |
| URL | https://arxiv.org/abs/q-bio/0505037 |
| DOI | 10.1529/biophysj.104.057158 |
Abstract
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.
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"abstract": "Trypsin and chymotrypsin are both serine proteases with high sequence and\nstructural similarities, but with different substrate specificity. Previous\nexperiments have demonstrated the critical role of the two loops outside the\nbinding pocket in controlling the specificity of the two enzymes. To understand\nthe mechanism of such a control of specificity by distant loops, we have used\nthe Gaussian Network Model to study the dynamic properties of trypsin and\nchymotrypsin and the roles played by the two loops. A clustering method was\nintroduced to analyze the correlated motions of residues. We have found that\ntrypsin and chymotrypsin have distinct dynamic signatures in the two loop\nregions which are in turn highly correlated with motions of certain residues in\nthe binding pockets. Interestingly, replacing the two loops of trypsin with\nthose of chymotrypsin changes the motion style of trypsin to chymotrypsin-like,\nwhereas the same experimental replacement was shown necessary to make trypsin\nhave chymotrypsin\u0027s enzyme specificity and activity. These results suggest that\nthe cooperative motions of the two loops and the substrate-binding sites\ncontribute to the activity and substrate specificity of trypsin and\nchymotrypsin.",
"arxiv_id": "q-bio/0505037",
"authors": [
"Wenzhe Ma",
"Chao Tang",
"Luhua Lai"
],
"categories": [
"q-bio.BM"
],
"doi": "10.1529/biophysj.104.057158",
"title": "Specificity of Trypsin and Chymotrypsin: Loop Motion Controlled Dynamic Correlation as a Determinant",
"url": "https://arxiv.org/abs/q-bio/0505037"
},
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