Structural highlights
Publication Abstract from PubMed
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.
Transition states. Trapping a transition state in a computationally designed protein bottle.,Pearson AD, Mills JH, Song Y, Nasertorabi F, Han GW, Baker D, Stevens RC, Schultz PG Science. 2015 Feb 20;347(6224):863-7. doi: 10.1126/science.aaa2424. PMID:25700516[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pearson AD, Mills JH, Song Y, Nasertorabi F, Han GW, Baker D, Stevens RC, Schultz PG. Transition states. Trapping a transition state in a computationally designed protein bottle. Science. 2015 Feb 20;347(6224):863-7. doi: 10.1126/science.aaa2424. PMID:25700516 doi:http://dx.doi.org/10.1126/science.aaa2424
