Binding and Interaction of Dinitroanilines with Apicomplexan and Kinetoplastid Alpha-tubulin.
From: Department of Chemical Engineering, Center for Computational Biology, Washington University, St. Louis, Missouri 63130-4899, USA.
Journal of medicinal chemistry
- Publish Date: Aug 2006
- ISSN: 0022-2623
- Volume: 49
- Issue: 17
- Pages: 5226-31
- Medium: Print
- Language: English
- Citation (JAMA): Mitra Arpita, Sept David, et al. Binding and Interaction of Dinitroanilines with Apicomplexan and Kinetoplastid Alpha-tubulin.. J. Med. Chem. Aug 2006;49:5226-31
Abstract
Despite years of use as commercial herbicides, it is still unclear how dinitroanilines interact with tubulin, how they cause microtubule disassembly, and why they are selectively active against plant and protozoan tubulin. In this work, through a series of computational studies, a common binding site of oryzalin, trifluralin, and GB-II-5 on apicomplexan and kinetoplastid alpha-tubulin is proposed. Furthermore, to investigate how dinitroanilines affect tubulin dynamics, molecular dynamics simulations of Leishmania alpha-tubulin with and without a bound dinitroaniline are performed. The results obtained provide insight into the molecular mechanism by which these compounds interact with tubulin and function to prevent microtubule assembly. Finally, to aid in the design of effective parasitic microtubule inhibitors, several novel dinitroaniline analogues are evaluated. The location of the binding site and the relative binding affinities of the dinitroanilines all agree well with experimental data.
Mesh Headings (Keywords): Aniline Compounds, Animals, Apicomplexa, Binding Sites, Binding, Competitive, Dinitrobenzenes, Kinetoplastida, Molecular Structure, Protein Conformation, Protein Structure, Tertiary, Structure-Activity Relationship, Sulfanilamides, Trifluralin, Tubulin
Check for Full Text / PubMed Unique Identifier (PMID): 16913711
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.