{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:18:01Z","timestamp":1785863881153,"version":"3.56.0"},"reference-count":89,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T00:00:00Z","timestamp":1572220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>(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\u2013function 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.<\/jats:p>","DOI":"10.3390\/toxins11110625","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T11:26:13Z","timestamp":1572261973000},"page":"625","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Sequence and a Three-Dimensional Structural Analysis Reveal Substrate Specificity among Snake Venom Phosphodiesterases"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3793-7393","authenticated-orcid":false,"given":"Anwar","family":"Ullah","sequence":"first","affiliation":[{"name":"Department of Biosciences, COMSATS University Islamabad, Park Road, Tarlai Kalan, Islamabad 45550, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kifayat","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University Islamabad, Park Road, Tarlai Kalan, Islamabad 45550, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University Islamabad, Park Road, Tarlai Kalan, Islamabad 45550, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Betzel","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0589-1896","authenticated-orcid":false,"given":"Shafiq","family":"ur Rehman","sequence":"additional","affiliation":[{"name":"Department of Botany, University of Okara, Okara 56300, Punjab, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.1111\/j.1742-4658.2011.08115.x","article-title":"Enzymatic toxins from snake venom: Structural characterization and mechanism of catalysis","volume":"278","author":"Kang","year":"2011","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.ijbiomac.2018.03.164","article-title":"Thrombin-like enzymes from snake venom: Structural characterization and mechanism of action","volume":"114","author":"Ullah","year":"2018","journal-title":"Int. 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