Loading...
Please wait, while we are loading the content...
Synthesis and folding of a mirror-image enzyme reveals ambidextrous chaperone activity.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Weinstock, Matthew T. Jacobsen, Michael T. Kay, Michael S. |
| Copyright Year | 2014 |
| Abstract | Mirror-image proteins (composed of D-amino acids) are promising therapeutic agents and drug discovery tools, but as synthesis of larger D-proteins becomes feasible, a major anticipated challenge is the folding of these proteins into their active conformations. In vivo, many large and/or complex proteins require chaperones like GroEL/ES to prevent misfolding and produce functional protein. The ability of chaperones to fold D-proteins is unknown. Here we examine the ability of GroEL/ES to fold a synthetic d-protein. We report the total chemical synthesis of a 312-residue GroEL/ES-dependent protein, DapA, in both L- and D-chiralities, the longest fully synthetic proteins yet reported. Impressively, GroEL/ES folds both L- and D-DapA. This work extends the limits of chemical protein synthesis, reveals ambidextrous GroEL/ES folding activity, and provides a valuable tool to fold d-proteins for drug development and mirror-image synthetic biology applications. |
| File Format | PDF HTM / HTML |
| DOI | 10.1073/pnas.1410900111 |
| PubMed reference number | 25071217 |
| Journal | Medline |
| Volume Number | 111 |
| Issue Number | 32 |
| Alternate Webpage(s) | http://www.biochem.utah.edu/kay/images/uploads/PNAS-2014-Weinstock.pdf |
| Alternate Webpage(s) | http://www.slas.ac.cn/upload/20141127-4.pdf |
| Alternate Webpage(s) | https://doi.org/10.1073/pnas.1410900111 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
