Volume 6 Supplement 1

9th German Conference on Chemoinformatics

Open Access

Evaluation of molecular model-based discovery of ecto-5’-nucleotidase inhibitors on the basis of X-ray structures

  • Norbert Furtmann1 and
  • Jürgen Bajorath1
Journal of Cheminformatics20146(Suppl 1):P13

DOI: 10.1186/1758-2946-6-S1-P13

Published: 11 March 2014

Ecto-5’-nucleotidase (e5NT) belongs to the family of metallophosphoesterases, hydrolyses AMP to adenosine, and is a regulator of the adenosine signaling pathway [1]. It has been shown, that free adenosine is involved in various diseases and cancer progression [2, 3]. In a previous study, a molecular model of e5NT has been created and used for the identification of new sulfonamide inhibitors [4]. Recently, X-ray structures of human e5NT in complex with different inhibitors were published [5]. This made it possible to reevaluate the model building and virtual screening efforts in detail. An extensive analysis of the comparative e5NT model, built using a bacterial enzyme in the presence of 35% sequence identity as a template, showed that the model was topologically correct and had high accuracy within the active site region. Comparative docking studies were carried out to explore inhibitor binding characteristics within the X-ray structure and the model. The results provided plausible explanations for the successful identification of new e5NT inhibitors by model-based virtual screening and highlighted important parameters [6].

Authors’ Affiliations

(1)
Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität

References

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Copyright

© Furtmann and Bajorath; licensee Chemistry Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.