Baird, Wm. Vance , Nyporko, Alexej Yu. , Yemets, Alla I. , Blume, Yaroslav B. .
Modeling herbicide binding to tubulin in three-dimensions.
Tubulins, the fundamental component of microtubules, appear to be the target site for a number of mitotic-disrupter drugs (e.g., dinitroanilines, phosphoroamidates, benzamides and carbamates). Mutations in alpha- or beta-tubulins have been shown to correlate with or confer resistance to these various anti-microtubule compounds. We report the preliminary 3-D modeling of wild type and mutant alpha-tubulin from goosegrass (Eleusine indica), based upon a published 3.7 Å density crystalline structure obtained for porcine tubulin. This reconstruction allowed spatial docking of 3-D models of trifluralin and amiprophosmethyl herbicides onto the tubulin surface represented by electrostatic potential. Further analysis identified a positively charged cavity on the inter-dimer contact face to which the herbicide molecules bound (via their NO2- groups) with minimal energy. This interactive cavity possesses a large net-positive charge in the wild type alpha-tubulin. When 3-D reconstructions of mutant alpha-tubulins (gene sequences cloned from plants resistant to oryzalin) were used in docking experiments, the herbicides failed to bind. The cavity in these preliminary models had a reduced positive charge and its conformation was altered significantly. We identified specific amino acid residues of alpha-tubulin that appear to play a critical role in herbicide binding. Such studies will enhance our understanding of the mechanism of herbicide resistance and provide a system for herbicide design and testing.
1 - Clemson University, Horticulture, Poole Agric. Center, Clemson, South Carolina, 29634-0319, U.S.A.
2 - National Academy of Sciences of Ukraine, Institute of Cell Biology and Genetic Engineering, acad. Zabolotnogo str., 148, Kiev, 03143, Ukraine
Presentation Type: Poster
Location: Special Event Center (Cliff Lodge)
Date: Tuesday, August 3rd, 2004
Time: 12:30 PM