Interactions of the male contraceptive target EPPIN with semenogelin-1 and small organic ligands

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade Estadual de Campinas (UNICAMP)-
Autor(es): dc.contributorEppin Pharma Inc.-
Autor(es): dc.contributorUniversity of North Carolina at Chapel Hill-
Autor(es): dc.contributorUniversidade Federal do Rio de Janeiro (UFRJ)-
Autor(es): dc.creatorGomes, Antoniel A. S.-
Autor(es): dc.creatorSantos, Natália C. M.-
Autor(es): dc.creatorRosa, Leonardo R.-
Autor(es): dc.creatorBorges, Rafael J.-
Autor(es): dc.creatorFontes, Marcos R. M.-
Autor(es): dc.creatorHamil, Katherine G.-
Autor(es): dc.creatorO’Rand, Michael G.-
Autor(es): dc.creatorSilva, Erick J. R.-
Data de aceite: dc.date.accessioned2025-08-21T22:49:00Z-
Data de disponibilização: dc.date.available2025-08-21T22:49:00Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2023-11-30-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1038/s41598-023-41365-1-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/300352-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/300352-
Descrição: dc.descriptionNovel male contraceptives will promote gender equality in sharing contraceptive responsibility. The sperm-associated protein epididymal protease inhibitor (EPPIN) is a promising target for non-hormonal male contraception. EPPIN interacts with the semen coagulum protein semenogelin-1 (SEMG1) on the sperm surface, leading to transient inhibition of sperm motility after ejaculation. Small organic molecules targeting EPPIN's SEMG1-binding are under development as male contraceptives. Here, we combined computational approaches to uncover key aspects underlying EPPIN binding to SEMG1 and small organic ligands. We generated a human EPPIN model showing a typical arrangement of the WFDC (Whey-acid four disulfide core)-type and Kunitz-type domains, connected by a hinge region. Determining the EPPIN model's intrinsic motion by molecular dynamics simulations and normal mode analysis revealed a conformation, presenting a binding pocket that accommodates SEMG1Glu229-Gln247, EP055, and EP012. EPPIN's residues Phe63 and Lys68 (WFDC domain), Asp71 (hinge region), and Asn113, Asn114, and Asn115 (Kunitz domain) were identified as hot spots for SEMG1, EP055, and EP012 binding. Moreover, hydrophobic and hydrophilic residues in the WFDC and Kunitz domains allow plasma membrane anchoring, orienting the EPPIN binding pocket to the solvent. Targeting EPPIN's essential residues for its biomolecular interactions may improve the rational design of EPPIN ligands as spermiostatic compounds.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)-
Descrição: dc.descriptionDepartment of Biophysics and Pharmacology Institute of Biosciences of Botucatu São Paulo State University, SP-
Descrição: dc.descriptionThe Center of Medicinal Chemistry (CQMED) Center for Molecular Biology and Genetic Engineering (CBMEG) University of Campinas (UNICAMP)-
Descrição: dc.descriptionInstitute for Advanced Studies of the Sea (IEAMAR) São Paulo State University UNESP, SP-
Descrição: dc.descriptionResearch and Development Eppin Pharma Inc.-
Descrição: dc.descriptionDepartment of Cell Biology and Physiology University of North Carolina at Chapel Hill-
Descrição: dc.descriptionLaboratory of Biological Physics Carlos Chagas Filho Institute of Biophysics Universidade Federal do Rio de Janeiro, RJ-
Descrição: dc.descriptionDepartment of Biophysics and Pharmacology Institute of Biosciences of Botucatu São Paulo State University, SP-
Descrição: dc.descriptionInstitute for Advanced Studies of the Sea (IEAMAR) São Paulo State University UNESP, SP-
Descrição: dc.descriptionFAPESP: 2015/08227-0-
Descrição: dc.descriptionFAPESP: 2023/04496-2-
Descrição: dc.descriptionCNPq: 303616/2022-9-
Descrição: dc.descriptionCAPES: 88882.183574/2017-01-
Idioma: dc.languageen-
Relação: dc.relationScientific Reports-
???dc.source???: dc.sourceScopus-
Título: dc.titleInteractions of the male contraceptive target EPPIN with semenogelin-1 and small organic ligands-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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