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Open AccessArticle

The Sequence and a Three-Dimensional Structural Analysis Reveal Substrate Specificity among Snake Venom Phosphodiesterases

1
Department of Biosciences, COMSATS University Islamabad, Park Road, Tarlai Kalan, Islamabad 45550, Pakistan
2
Institute of Biochemistry and Molecular Biology, University of Hamburg, Laboratory for Structural Biology of Infection and Inflammation, c/o DESY. Build. 22a, Notkestrasse 85, 22607 Hamburg, Germany
3
Department of Botany, University of Okara, Okara 56300, Punjab, Pakistan
*
Authors to whom correspondence should be addressed.
Toxins 2019, 11(11), 625; https://doi.org/10.3390/toxins11110625
Received: 25 July 2019 / Revised: 21 August 2019 / Accepted: 3 September 2019 / Published: 28 October 2019
(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–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. View Full-Text
Keywords: snake venom; phosphodiesterases; amino acid sequence and three-dimensional structural analysis; variable substrate specificity; PDE_Ca structure–function relationship snake venom; phosphodiesterases; amino acid sequence and three-dimensional structural analysis; variable substrate specificity; PDE_Ca structure–function relationship
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Ullah, A.; Ullah, K.; Ali, H.; Betzel, C.; ur Rehman, S. The Sequence and a Three-Dimensional Structural Analysis Reveal Substrate Specificity among Snake Venom Phosphodiesterases. Toxins 2019, 11, 625.

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