The Sequence and a Three-Dimensional Structural Analysis Reveal Substrate Specificity Among Snake Venom Phosphodiesterases
| Autor: | Christian Betzel, Shafiq ur Rehman, Anwar Ullah, Hamid Ali, Kifayat Ullah |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Platelet Aggregation
Health Toxicology and Mutagenesis lcsh:Medicine Venom Toxicology complex mixtures Article Substrate Specificity Structure-Activity Relationship 03 medical and health sciences Somatomedin B Crotalid Venoms Animals Amino Acid Sequence phosphodiesterases PDE_Ca structure–function relationship Envenomation 030304 developmental biology snake venom chemistry.chemical_classification 0303 health sciences Molecular Structure biology Phosphoric Diester Hydrolases Chemistry Crotalus lcsh:R 030302 biochemistry & molecular biology variable substrate specificity Active site Phosphodiesterase MODELLER Enzyme Biochemistry Snake venom pde_ca structure–function relationship biology.protein amino acid sequence and three-dimensional structural analysis |
| Zdroj: | Toxins Volume 11 Issue 11 Toxins, Vol 11, Iss 11, p 625 (2019) |
| ISSN: | 2072-6651 |
| DOI: | 10.3390/toxins11110625 |
| Popis: | (1) Background. Snake venom phosphodiesterases (SVPDEs) are among the least studied venom enzymes. In envenomation, they display various pathological effects, including induction of hypotension, inhibition of platelet aggregation, edema, and paralysis. Until now, there have been no 3D structural studies of these enzymes, thereby preventing structure&ndash function analysis. To enable such investigations, the present work describes the model-based structural and functional characterization of a phosphodiesterase from Crotalus adamanteus venom, named PDE_Ca. (2) Methods. The PDE_Ca structure model was produced and validated using various software (model building: I-TESSER, MODELLER 9v19, Swiss-Model, and validation tools: PROCHECK, ERRAT, Molecular Dynamic Simulation, and Verif3D). (3) Results. The proposed model of the enzyme indicates that the 3D structure of PDE_Ca comprises four domains, a somatomedin B domain, a somatomedin B-like domain, an ectonucleotide pyrophosphatase domain, and a DNA/RNA non-specific domain. Sequence and structural analyses suggest that differences in length and composition among homologous snake venom sequences may account for their differences in substrate specificity. Other properties that may influence substrate specificity are the average volume and depth of the active site cavity. (4) Conclusion. Sequence comparisons indicate that SVPDEs exhibit high sequence identity but comparatively low identity with mammalian and bacterial PDEs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |