Backbone Flexibility Controls the Activity and Specificity of a Protein−Protein Interface: Specificity in Snake Venom Metalloproteases
| Autor: | Klaus R. Liedl, José María Gutiérrez, Irmgard Merfort, Hannes G. Wallnoefer, Torsten Lingott |
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| Rok vydání: | 2010 |
| Předmět: |
Snake venom
Flexibility (anatomy) Protein Conformation Snake Molecular Sequence Data Nanotechnology Molecular Dynamics Simulation Crystallography X-Ray Biochemistry Catalysis Amino acid sequence Colloid and Surface Chemistry Sequence alignment Molecular sequence data Molecular dynamics simulation medicine Animals Protein binding Amino Acid Sequence Protein interface Metalloproteinase Chemistry A protein Snakes General Chemistry Sequence homology medicine.anatomical_structure Protein conformation Metalloproteases Biophysics Sequence Alignment Function (biology) Protein Binding Snake Venoms |
| Zdroj: | Journal of the America Chemical Society; Volumen 132, Número 30. 2010 Kérwá Universidad de Costa Rica instacron:UCR |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/ja909908y |
| Popis: | Protein-protein interfaces have crucial functions in many biological processes. 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. A perfect paradigm to study such multispecific protein-protein interfaces are snake venom metalloproteases (SVMPs). 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. We present computer simulations indicating 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. 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. UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP) |
| Databáze: | OpenAIRE |
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