Structural, enzymatic and pharmacological profiles of AplTX-II - A basic sPLA(2) (D49) isolated from the Agkistrodon piscivorus leucostoma snake venom

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Resende, LM (Author) Other; Almeida, JR (Author) Other; Guaraca Medina, TA (Author) Other; Viegas, MF (Author) Other; Soares, AM (Author) Other; Ramos, MJ (Author) Other; Pedro A Fernandes (Author) FCUP; Marangoni, S (Author) Other; Da Silva, SL (Author) Other

Journal

Title: International Journal of Biological Macromolecules

Vol. 175

Pages: 572-585

ISSN: 0141-8130

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 2 Citations

Other information

Authenticus ID: P-00T-G75

DOI: 10.1016/j.ijbiomac.2021.01.187

Abstract (EN): A basic sPLA(2) (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 sPLA(2)s revealed that AplTX-II presented all the structural reasons expected for a basic sPLA(2)s. 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 sPLA(2) 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14