PNP Diminishes Guanosine Glycosidic Bond Strength Through Restrictive Ring Pucker as a Precursor to Phosphorylation
| dc.contributor.author | Barnett, Christopher B | |
| dc.contributor.author | Naidoo, Kevin J | |
| dc.date.accessioned | 2016-08-24T13:05:45Z | |
| dc.date.available | 2016-08-24T13:05:45Z | |
| dc.date.issued | 2013 | |
| dc.date.updated | 2016-08-24T13:04:26Z | |
| dc.description.abstract | Purine nucleoside phosphorylase is a transferase that catalyzes the addition of phosphate and removal of a purine base from guanosine and similar nucleosides. Here the interplay between sugar puckering conformation, the enzyme, and the perceived course of the reaction is examined using QM/MM FEARCF dynamics simulations. The enzyme biases the guanosine sugar ring toward a flattened 4E conformer as a step that is critical to the success of the phosphorylation reaction. The C4′ endo conformer allows the nonbonded ring oxygen orbital to align and donate electrons into the antibonding glycosidic bond orbital, thus weakening the bond. This conformational preference is due to sustained and directed noncovalent interactions anchored by the phosphate nucleophile’s hydrogen bonds to the sugar C2′ and C3′ hydroxyls. In so doing, PNP alters the solution sugar ring pucker preferences as part of its catalytic reaction barrier lowering function. | en_ZA |
| dc.identifier | http://dx.doi.org/10.1021/jp3109013 | |
| dc.identifier.apacitation | Barnett, C. B., & Naidoo, K. J. (2013). PNP Diminishes Guanosine Glycosidic Bond Strength Through Restrictive Ring Pucker as a Precursor to Phosphorylation. <i>The Journal of Physical Chemistry</i>, http://hdl.handle.net/11427/21519 | en_ZA |
| dc.identifier.chicagocitation | Barnett, Christopher B, and Kevin J Naidoo "PNP Diminishes Guanosine Glycosidic Bond Strength Through Restrictive Ring Pucker as a Precursor to Phosphorylation." <i>The Journal of Physical Chemistry</i> (2013) http://hdl.handle.net/11427/21519 | en_ZA |
| dc.identifier.citation | Barnett, C. B., & Naidoo, K. J. (2013). PNP Diminishes Guanosine Glycosidic Bond Strength Through Restrictive Ring Pucker as a Precursor to Phosphorylation. The Journal of Physical Chemistry B, 117(20), 6019-6026. | en_ZA |
| dc.identifier.issn | 0022-3654 | en_ZA |
| dc.identifier.ris | TY - Journal Article AU - Barnett, Christopher B AU - Naidoo, Kevin J AB - Purine nucleoside phosphorylase is a transferase that catalyzes the addition of phosphate and removal of a purine base from guanosine and similar nucleosides. Here the interplay between sugar puckering conformation, the enzyme, and the perceived course of the reaction is examined using QM/MM FEARCF dynamics simulations. The enzyme biases the guanosine sugar ring toward a flattened 4E conformer as a step that is critical to the success of the phosphorylation reaction. The C4′ endo conformer allows the nonbonded ring oxygen orbital to align and donate electrons into the antibonding glycosidic bond orbital, thus weakening the bond. This conformational preference is due to sustained and directed noncovalent interactions anchored by the phosphate nucleophile’s hydrogen bonds to the sugar C2′ and C3′ hydroxyls. In so doing, PNP alters the solution sugar ring pucker preferences as part of its catalytic reaction barrier lowering function. DA - 2013 DB - OpenUCT DP - University of Cape Town J1 - The Journal of Physical Chemistry LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 SM - 0022-3654 T1 - PNP Diminishes Guanosine Glycosidic Bond Strength Through Restrictive Ring Pucker as a Precursor to Phosphorylation TI - PNP Diminishes Guanosine Glycosidic Bond Strength Through Restrictive Ring Pucker as a Precursor to Phosphorylation UR - http://hdl.handle.net/11427/21519 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/21519 | |
| dc.identifier.uri | http://pubs.acs.org/doi/abs/10.1021/jp3109013 | |
| dc.identifier.vancouvercitation | Barnett CB, Naidoo KJ. PNP Diminishes Guanosine Glycosidic Bond Strength Through Restrictive Ring Pucker as a Precursor to Phosphorylation. The Journal of Physical Chemistry. 2013; http://hdl.handle.net/11427/21519. | en_ZA |
| dc.language | eng | en_ZA |
| dc.publisher | The Journal of Physical Chemistry | en_ZA |
| dc.publisher.institution | University of Cape Town | |
| dc.source | The Journal of Physical Chemistry | en_ZA |
| dc.source.uri | http://pubs.acs.org/journal/jpcbfk | |
| dc.subject.other | Guanosine | |
| dc.subject.other | Glycosidic | |
| dc.subject.other | Precursor | |
| dc.subject.other | Phosphorylation | |
| dc.title | PNP Diminishes Guanosine Glycosidic Bond Strength Through Restrictive Ring Pucker as a Precursor to Phosphorylation | 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 |