Reaction Mechanism of O-GlcNAc Transferase Explored By QM/MM Molecular Dynamics
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| Year of publication | 2016 |
| Type | Conference abstract |
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| Description | Carbohydrates are ubiquitously present in all cells in the variety of forms e.g. glyco-conjugates, playing a pivotal role in a plethora of the biological processes. These glyco-conjugates are formed by glycosyltransferases, which add saccharides onto proteins, lipids, sugars, etc. The inverting glycosyltransferase O-GlcNAc transferase (OGT) post-translationally modifies a variety of proteins. The misregulation of O-GlcNAc-ylation is linked to a wide range of diseases, so knowing its reaction mechanism is very significant. Known OGT structures and experimental biochemical data suggest several possible mechanisms. In the present study, all experimentally proposed mechanisms with native UDP-GlcNAc and sulphur analogue UDP-5-S-GlcNAc donor substrate were investigated at the DFT QM/MM level. The sophisticated theoretical approaches such as hybrid QM/MM DFT Carr-Parinello ab initio molecular dynamics combined with a string method for reaction path optimization were used to investigate which of the three proposed mechanisms might be the most probable. |
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