{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T13:27:08Z","timestamp":1762608428308,"version":"3.37.3"},"reference-count":39,"publisher":"Portland Press Ltd.","issue":"19","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,15]]},"abstract":"<jats:p>Several Schistosoma species cause Schistosomiasis, an endemic disease in 78 countries that is ranked second amongst the parasitic diseases in terms of its socioeconomic impact and human health importance. The drug recommended for treatment by the WHO is praziquantel (PZQ), but there are concerns associated with PZQ, such as the lack of information about its exact mechanism of action, its high price, its effectiveness \u2014 which is limited to the parasite's adult form \u2014 and reports of resistance. The parasites lack the de novo purine pathway, rendering them dependent on the purine salvage pathway or host purine bases for nucleotide synthesis. Thus, the Schistosoma purine salvage pathway is an attractive target for the development of necessary and selective new drugs. In this study, the purine nucleotide phosphorylase II (PNP2), a new isoform of PNP1, was submitted to a high-throughput fragment-based hit discovery using a crystallographic screening strategy. PNP2 was crystallized and crystals were soaked with 827 fragments, a subset of the Maybridge 1000 library. X-ray diffraction data was collected and structures were solved. Out of 827-screened fragments we have obtained a total of 19 fragments that show binding to PNP2. Fourteen of these fragments bind to the active site of PNP2, while five were observed in three other sites. Here we present the first fragment screening against PNP2.<\/jats:p>","DOI":"10.1042\/bcj20210041","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T15:49:26Z","timestamp":1631807366000},"page":"3655-3670","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Crystallographic approach to fragment-based hit discovery against <i>Schistosoma mansoni<\/i> purine nucleoside phosphorylase"],"prefix":"10.1042","volume":"478","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3635-1246","authenticated-orcid":false,"given":"Muhammad","family":"Faheem","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biof\u00edsica Molecular, Departamento de Biologia Celular, Universidade de Bras\u00edlia, Bras\u00edlia, DF 70910-900, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Gen\u00f4micas e Biotecnologia, Universidade Cat\u00f3lica de Bras\u00edlia, SGAN 916 M\u00f3dulo B Avenida W5 - Asa Norte, Bras\u00edlia, DF, Brazil"},{"name":"Harwell Science and Innovation Campus, Fermi Ave, Didcot OX11 0DE, U.K."},{"name":"Department of Biological Sciences, National University of Medical Sciences, The Mall, Abid Majeed Rd, Rawalpindi, Punjab 46000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Napole\u00e3o","family":"Fonseca Valadares","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biof\u00edsica Molecular, Departamento de Biologia Celular, Universidade de Bras\u00edlia, Bras\u00edlia, DF 70910-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Brand\u00e3o-Neto","sequence":"additional","affiliation":[{"name":"Harwell Science and Innovation Campus, Fermi Ave, Didcot OX11 0DE, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dom","family":"Bellini","sequence":"additional","affiliation":[{"name":"Harwell Science and Innovation Campus, Fermi Ave, Didcot OX11 0DE, U.K."},{"name":"MRC LMB, Francis Crick Avenue, Cambridge CB2 0QH, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Collins","sequence":"additional","affiliation":[{"name":"Harwell Science and Innovation Campus, Fermi Ave, Didcot OX11 0DE, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas M.","family":"Pearce","sequence":"additional","affiliation":[{"name":"Harwell Science and Innovation Campus, Fermi Ave, Didcot OX11 0DE, U.K."},{"name":"Structural Genomics Consortium, Old Road Campus Research Build, Roosevelt Dr, Oxford OX3 7DQ, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Bird","sequence":"additional","affiliation":[{"name":"Harwell Science and Innovation Campus, Fermi Ave, Didcot OX11 0DE, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana","family":"Roberta Torini","sequence":"additional","affiliation":[{"name":"Instituto de F\u00edsica de S\u00e3o Carlos, Universidade de S\u00e3o Paulo, S\u00e3o Carlos, SP 13563-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond","family":"Owens","sequence":"additional","affiliation":[{"name":"Harwell Science and Innovation Campus, Fermi Ave, Didcot OX11 0DE, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Humberto","family":"DMuniz Pereira","sequence":"additional","affiliation":[{"name":"Instituto de F\u00edsica de S\u00e3o Carlos, Universidade de S\u00e3o Paulo, S\u00e3o Carlos, SP 13563-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Von Delft","sequence":"additional","affiliation":[{"name":"Harwell Science and Innovation Campus, Fermi Ave, Didcot OX11 0DE, U.K."},{"name":"Structural Genomics Consortium, Old Road Campus Research Build, Roosevelt Dr, Oxford OX3 7DQ, U.K."},{"name":"Department of Biochemistry, University of Johannesburg, Auckland Park 2006, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Alexandre Ribeiro Gon\u00e7alves","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biof\u00edsica Molecular, Departamento de Biologia Celular, Universidade de Bras\u00edlia, Bras\u00edlia, DF 70910-900, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Gen\u00f4micas e Biotecnologia, Universidade Cat\u00f3lica de Bras\u00edlia, SGAN 916 M\u00f3dulo B Avenida W5 - 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