Structural, enzymatic and pharmacological profiles of AplTX-II - A basic sPLA2 (D49) isolated from the Agkistrodon piscivorus leucostoma snake venom
| Autor: | L.M. Resende, Andreimar Martins Soares, Pedro A. Fernandes, Sergio Marangoni, Saulo L. da Silva, José R. Almeida, Tatiana A. Guaraca-Medina, Matilde F. Viegas, Maria J. Ramos |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Molecular model biology Chemistry Stereochemistry Protein primary structure Protein Data Bank (RCSB PDB) Substrate (chemistry) Venom 02 engineering and technology General Medicine Leucostoma 021001 nanoscience & nanotechnology biology.organism_classification Biochemistry 03 medical and health sciences Structural Biology Snake venom Homology modeling 0210 nano-technology Molecular Biology 030304 developmental biology |
| Zdroj: | International Journal of Biological Macromolecules. 175:572-585 |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2021.01.187 |
| Popis: | A basic sPLA2 (D49) from the venom of snake Agkistrodon piscivorus leucostoma (AplTX-II) was isolated, purified and characterized. We determined the enzymatic and pharmacological profiles of this toxin. AplTX-II was isolated with a high level of purity through reverse phase chromatography and molecular exclusion. The enzyme showed pI 9.48 and molecular weight of 14,003 Da. The enzymatic activity of the AplTX-II depended on Ca2+ pH and temperature. The comparison of the primary structure with other sPLA2s revealed that AplTX-II presented all the structural reasons expected for a basic sPLA2s. Additionally, we have resolved its structure with the docked synthetic substrate NOBA (4-nitro-3-octanoyloxy benzoic acid) by homology modeling, and performed MD simulations with explicit solvent. Structural similarities were found between the enzyme's modeled structure and other snake sPLA2 X-Ray structures, available in the PDB database. NOBA and active-site water molecules spontaneously adopted stable positions and established interactions in full agreement with the reaction mechanism, proposed for the physiological substrate, suggesting that NOBA hydrolysis is an excellent model to study phospholipid hydrolysis. |
| Databáze: | OpenAIRE |
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