Molecular details from computational reaction dynamics for the cellobiohydrolase I glycosylation reaction
| dc.contributor.author | Barnett, Christopher B | |
| dc.contributor.author | Wilkinson, Karl A | |
| dc.contributor.author | Naidoo, Kevin J | |
| dc.date.accessioned | 2016-08-22T11:15:08Z | |
| dc.date.available | 2016-08-22T11:15:08Z | |
| dc.date.issued | 2011 | |
| dc.date.updated | 2016-08-22T11:07:52Z | |
| dc.description.abstract | Glycosylation of cellobiose hydrolase I (CBHI), is a key step in the processing and degradation of cellulose. Here the pathways and barriers of the reaction are explored using the free energy from adaptive reaction coordinate forces (FEARCF) reaction dynamics method coupled with SCC-DFTB/MM. In many respects CBHI follows the expected general GH7 family mechanism that involves the Glu-X-Asp-X-X-Glu motif. However, critical electronic and conformational details, previously not known, were discovered through our computations. The central feature that ensures the success of the glycosylation reaction are the Glu212 nucleophile’s hydrogen bond to the hydroxyl on C2, of the glucose in the −1 position of the cellulosic strand. This Glu212 function restricts the C2 hydroxyl in such a way as to favor the formation of the 4E ring pucker of the −1 position glucose. A frontier molecular orbital analysis of the structures along the reaction surface proves the existence of an oxocarbenium ion, which has both transition state and intermediate character. The transition state structure is able to descend down the glycosylation pathway through the critical combination of Asp214 (HOMO), ring oxygen (LUMO), and Glu212 (HOMO), anomeric carbon (LUMO) interactions. Using the fully converged FEARCF SCC-DFTB/MM reaction surface, we find a barrier of 17.48 kcal/mol separating bound cellulose chain from the glycosylated CBHI. Taking recrossing into account gives kcat = 0.415 s–1 for cellobiohydrolase glycosylation. | en_ZA |
| dc.identifier | http://dx.doi.org/http://pubs.acs.org/doi/abs/10.1021/ja206842j | |
| dc.identifier.apacitation | Barnett, C. B., Wilkinson, K. A., & Naidoo, K. J. (2011). Molecular details from computational reaction dynamics for the cellobiohydrolase I glycosylation reaction. <i>Journal of the American Chemical Society</i>, http://hdl.handle.net/11427/21389 | en_ZA |
| dc.identifier.chicagocitation | Barnett, Christopher B, Karl A Wilkinson, and Kevin J Naidoo "Molecular details from computational reaction dynamics for the cellobiohydrolase I glycosylation reaction." <i>Journal of the American Chemical Society</i> (2011) http://hdl.handle.net/11427/21389 | en_ZA |
| dc.identifier.citation | Barnett, C. B., Wilkinson, K. A., & Naidoo, K. J. (2011). Molecular details from computational reaction dynamics for the cellobiohydrolase I glycosylation reaction. Journal of the American Chemical Society, 133(48), 19474-19482. | en_ZA |
| dc.identifier.ris | TY - Journal Article AU - Barnett, Christopher B AU - Wilkinson, Karl A AU - Naidoo, Kevin J AB - Glycosylation of cellobiose hydrolase I (CBHI), is a key step in the processing and degradation of cellulose. Here the pathways and barriers of the reaction are explored using the free energy from adaptive reaction coordinate forces (FEARCF) reaction dynamics method coupled with SCC-DFTB/MM. In many respects CBHI follows the expected general GH7 family mechanism that involves the Glu-X-Asp-X-X-Glu motif. However, critical electronic and conformational details, previously not known, were discovered through our computations. The central feature that ensures the success of the glycosylation reaction are the Glu212 nucleophile’s hydrogen bond to the hydroxyl on C2, of the glucose in the −1 position of the cellulosic strand. This Glu212 function restricts the C2 hydroxyl in such a way as to favor the formation of the 4E ring pucker of the −1 position glucose. A frontier molecular orbital analysis of the structures along the reaction surface proves the existence of an oxocarbenium ion, which has both transition state and intermediate character. The transition state structure is able to descend down the glycosylation pathway through the critical combination of Asp214 (HOMO), ring oxygen (LUMO), and Glu212 (HOMO), anomeric carbon (LUMO) interactions. Using the fully converged FEARCF SCC-DFTB/MM reaction surface, we find a barrier of 17.48 kcal/mol separating bound cellulose chain from the glycosylated CBHI. Taking recrossing into account gives kcat = 0.415 s–1 for cellobiohydrolase glycosylation. DA - 2011 DB - OpenUCT DP - University of Cape Town J1 - Journal of the American Chemical Society LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - Molecular details from computational reaction dynamics for the cellobiohydrolase I glycosylation reaction TI - Molecular details from computational reaction dynamics for the cellobiohydrolase I glycosylation reaction UR - http://hdl.handle.net/11427/21389 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/21389 | |
| dc.identifier.uri | http://pubs.acs.org/doi/abs/10.1021/ja206842j | |
| dc.identifier.vancouvercitation | Barnett CB, Wilkinson KA, Naidoo KJ. Molecular details from computational reaction dynamics for the cellobiohydrolase I glycosylation reaction. Journal of the American Chemical Society. 2011; http://hdl.handle.net/11427/21389. | en_ZA |
| dc.language | eng | en_ZA |
| dc.publisher | American Chemical Society | en_ZA |
| dc.publisher.institution | University of Cape Town | |
| dc.source | Journal of the American Chemical Society | en_ZA |
| dc.source.uri | http://pubs.acs.org/journal/jacsat | |
| dc.subject.other | Molecular details | |
| dc.subject.other | computational reaction dynamics | |
| dc.subject.other | cellobiohydrolase | |
| dc.subject.other | glycosylation reaction | |
| dc.title | Molecular details from computational reaction dynamics for the cellobiohydrolase I glycosylation reaction | en_ZA |
| dc.type | Journal Article | en_ZA |
| uct.type.filetype | Text | |
| uct.type.filetype | Image | |
| uct.type.publication | Research | en_ZA |
| uct.type.resource | Article | en_ZA |