2000 Global Researcher Conference Proceeding
March 10 - 12, 2000
| Conference: | 2000 Global Researcher Conference |
|---|---|
| Title: | A proposal for the building and maintenance of an AVPR2 molecular model database |
| Authors: | Chini, Bice; Fanelli, Francesca; Marazza, Marco; Accomazzi, Luca |
| Institutions: | CNR Institute of Neuroscience, University of Modena, Simurg |
More than 100 mutations in the AVPR2 gene have been described in the last few years as responsible for X-linked forms of Nephrogenic Diabetes Insipidus. Even though a number of these mutations have been reproduced in vitro and their functional properties have been extensively investigated, we still lack a tridimensional V2 receptor model whose easy and free access may help our understanding of the structure/function defects of the known V2 receptor mutants. We have recently built a molecular model of the human OTR receptor in its free and agonist-bound as well as in its constitutively active and inactive states (F. Fanelli, P. Barbier, D. Zanchetta, P. G. De Benedetti and B. Chini (1999) Mol. Pharm. 56:214-225), and we will discuss the rationale for developing a similar model for the V2 receptor protein. Furthermore, since the formation of V2 receptor dimers / multimers has been shown to play an important role in determining the fate of co-expressed wild-type and mutant V2 receptors, we think that mapping the receptor regions involved in receptor oligomerization may aid the planning of successful gene therapy approaches aimed at the rescue of mutants V2 receptors. To this purpose, we plan to build molecular models of V2 dimers as already done for the a1b-adrenergic receptor (F. Fanelli, M. C. Menziani, A. Scheer, S. Cotecchia and P. G. De Benedetti (1999 ) International Journal of Quantum Chemistry, 73: 71-83). A database containing the V2 molecular models in the form of pdb files will be organized and its access will be made freely available to the scientific community; finally, we will provide a service aimed at the construction of V2 receptor mutants of particular interest.
Chini, et al., propose to construct a three dimensional model of the vasopressin-2 receptor (V2R). They think it will help researchers understand the structure/function defects in V2R mutants. The researchers state that building molecular models of V2R dimers will aid in developing therapeutic interventions that functionally rescue mutant V2Rs. The researchers also propose to develop a database of V2R molecular models, including V2R mutant models of interest to researchers, which will be freely available to the scientific community.