Volume 3 Supplement 1

6th German Conference on Chemoinformatics, GCC 2010

Open Access

Backbone flexibility controls the activity and specificity of a protein-protein interface – specificity in snake venom metalloproteases (SVMPs)

  • Hannes G Wallnoefer1,
  • Torsten Lingott2,
  • José María Gutiérrez3,
  • Irmgard Merfort2 and
  • Klaus R Liedl1Email author
Journal of Cheminformatics20113(Suppl 1):O22

https://doi.org/10.1186/1758-2946-3-S1-O22

Published: 19 April 2011

Protein-Protein interfaces have crucial functions in many biological processes [1]. The large interaction areas of such interfaces show complex interaction motifs. Even more challenging is the understanding of (multi-)specificity in protein-protein binding. Many proteins can bind several partners to mediate their function [2].

A perfect paradigm to study such multi-specific protein-protein interfaces are snake venom metalloproteases (SVMPs) [3]. Inherently, they bind to a variety of basement membrane proteins of capillaries, hydrolyze them, and induce profuse bleeding. However, despite having a high sequence homology, some SVMPs show a strong hemorrhagic activity, while others are (almost) inactive [4].

Our results indicate that the activity to induce hemorrhage, and thus the capability to bind the potential reaction partners, is related to the backbone flexibility in a certain surface region[4]. A subtle interplay between flexibility and rigidity of two loops seems to be the prerequisite for the proteins to carry out their damaging function. Presumably, a significant alteration in the backbone dynamics makes the difference between SVMPs that induce hemorrhage and the inactive ones.

Authors’ Affiliations

(1)
Institute of General, Inorganic and Theoretical Chemistry, Faculty of Chemistry and Pharmacy, University of Innsbruck
(2)
Institute of Pharmaceutical Sciences, Department of Pharmaceutical Biology and Biotechnology, University of Freiburg
(3)
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica

References

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  3. Bjarnason JB, Fox JW: Hemorrhagic metalloproteinases from snake venoms. Pharmac Ther. 1994, 62: 325-372. 10.1016/0163-7258(94)90049-3.View ArticleGoogle Scholar
  4. Wallnoefer HG, Lingott T, Gutiérrez JM, Merfort I, Liedl KR: Backbone Flexibility Controls the Activity and Specificity of a Protein - Protein Interface: Specificity in Snake Venom Metalloproteases. J Am Chem Soc. 2010, 132: 10330-10337. 10.1021/ja909908y.View ArticleGoogle Scholar

Copyright

© Wallnoefer et al; licensee BioMed Central Ltd. 2011

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.