| Autor: |
Cachau, R., Howard, E., Barth, P., Mitschler, A., Chevrier, B., Lamour, V., Joachimiak, A., Sanishvili, R., Van Zandt, M., Sibley, E., Moras, D., Podjarny, A., Cachau, R., Howard, E., Barth, P., Mitschler, A., Chevrier, B., Lamour, V., Joachimiak, A., Sanishvili, R., Van Zandt, M., Sibley, E., Moras, D., Podjarny, A. |
| Zdroj: |
Journal de Physique IV - Proceedings; September 2000, Vol. 10 Issue: 1 pPr10-3-Pr10-13, 31004p |
| Abstrakt: |
Aldose Reductase is an enzyme involved in diabetic complications, thoroughly studied for the purpose of inhibitor development. The structure of an enzyme-inhibitor complex solved at sub-atomic resolution has been used to develop a model for the catalytic mechanism. This model has been refined using a combination of Molecular Dynamics and Quantum calculations. It shows that the proton donation, the subject of previous controversies, is the combined effect of three residues : Lys 77, Tyr 48 and His 110. Lys 77 polarises the Tyr 48 OH group, which donates the proton to His 110, which becomes doubly protonated. His 110 then moves and donates the proton to the substrate. The key information from the sub-atomic resolution structure is the orientation of the ring and the single protonation of the His 110 in the enzyme-inhibitor complex. This model is in full agreement with all available experimental data. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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