| Autor: |
Pearson, Aaron D., Mills, Jeremy H., Song, Yifan, Nasertorabi, Fariborz, Han, Gye Won, Baker, David, Stevens, Raymond C., Schultz, Peter G. |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Science (New York, N.Y.). 347(6224) |
| ISSN: |
1095-9203 |
| Popis: |
The fleeting lifetimes of the transition states (TSs) of chemical reactions make determination of their three-dimensional structures by diffraction methods a challenge. Here, we used packing interactions within the core of a protein to stabilize the planar TS conformation for rotation around the central carbon-carbon bond of biphenyl so that it could be directly observed by x-ray crystallography. The computational protein design software Rosetta was used to design a pocket within threonyl-transfer RNA synthetase from the thermophile Pyrococcus abyssi that forms complementary van der Waals interactions with a planar biphenyl. This latter moiety was introduced biosynthetically as the side chain of the noncanonical amino acid p-biphenylalanine. Through iterative rounds of computational design and structural analysis, we identified a protein in which the side chain of p-biphenylalanine is trapped in the energetically disfavored, coplanar conformation of the TS of the bond rotation reaction. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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