Insights on the inhibition properties of Jatromollistatin (a cyclic heptapeptide) against Crotalus adamanteus metalloendopeptidase using molecular docking analysis

Detalhes bibliográficos
Autor(a) principal: Jucá, Thiago Lustosa
Data de Publicação: 2022
Outros Autores: Ramos, Márcio Viana, Cilli, Eduardo Maffud [UNESP], Neto, Antônio Eufrásio Vieira, Mackessy, Stephen P., Monteiro-Moreira, Ana Cristina Oliveira
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1002/jmr.2957
http://hdl.handle.net/11449/230510
Resumo: Jatropha mollissima is endemic to Brazil and is used for traditional medicinal purposes, including the treatment of snakebite. In this study, latex obtained from this plant was fractioned using reversed-phase chromatography, and the fractions were then screened for peptides. A 755 g/mol peptide was obtained, and MS/MS analyses indicated it had a cyclic sequence (Pro-Leu-Gly-Val-Leu-Leu-Tyr). This peptide sequence was present in the Jatropha genome database, and an identity value of 90.71%, an E-value of 0.0, and a score of 883 with NO-associated protein 1/chloroplastic/mitochondria of Jatropha curcas were obtained from the NCBI nonredundant protein sequence (nr) database. Molecular docking analyses performed with the peptide against a metalloendopeptidase belonging to Crotalus adamanteus snake venom suggested the cyclic peptide establishes favorable interactions with the catalytic site of the enzyme. Therefore, it could inhibit enzyme catalysis. This belief was corroborated by the formation of 6 hydrogen bonds with the linear form of the peptide. Tighter complexation of the cyclic form (41 kcal/mol more energetic) revealed better spatial blocking. The linear form outperformed the cyclic form in complexing the required energy, recruiting more catalytic residues (6/2), and in establishing more hydrogen bonds (6/3). However, cyclic folding provided a more significant spatial block within the catalytic site. The set of results suggests that the cycle peptide, here called Jatromollistatin, which was previously described as jatrophidin and pohlianin A in two other species of Jatropha, is a promising candidate to inhibit venom proteases. This belief is corroborated by the topical use of the latex for initial treatment of snakebites.
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spelling Insights on the inhibition properties of Jatromollistatin (a cyclic heptapeptide) against Crotalus adamanteus metalloendopeptidase using molecular docking analysislatexlaticifersorbitidessnake venomsolid phase extractionJatropha mollissima is endemic to Brazil and is used for traditional medicinal purposes, including the treatment of snakebite. In this study, latex obtained from this plant was fractioned using reversed-phase chromatography, and the fractions were then screened for peptides. A 755 g/mol peptide was obtained, and MS/MS analyses indicated it had a cyclic sequence (Pro-Leu-Gly-Val-Leu-Leu-Tyr). This peptide sequence was present in the Jatropha genome database, and an identity value of 90.71%, an E-value of 0.0, and a score of 883 with NO-associated protein 1/chloroplastic/mitochondria of Jatropha curcas were obtained from the NCBI nonredundant protein sequence (nr) database. Molecular docking analyses performed with the peptide against a metalloendopeptidase belonging to Crotalus adamanteus snake venom suggested the cyclic peptide establishes favorable interactions with the catalytic site of the enzyme. Therefore, it could inhibit enzyme catalysis. This belief was corroborated by the formation of 6 hydrogen bonds with the linear form of the peptide. Tighter complexation of the cyclic form (41 kcal/mol more energetic) revealed better spatial blocking. The linear form outperformed the cyclic form in complexing the required energy, recruiting more catalytic residues (6/2), and in establishing more hydrogen bonds (6/3). However, cyclic folding provided a more significant spatial block within the catalytic site. The set of results suggests that the cycle peptide, here called Jatromollistatin, which was previously described as jatrophidin and pohlianin A in two other species of Jatropha, is a promising candidate to inhibit venom proteases. This belief is corroborated by the topical use of the latex for initial treatment of snakebites.Experimental Biology Centre (NUBEX) University of Fortaleza (UNIFOR)Federal University of Ceara (UFC) Biochemistry and Molecular Biology DepartmentDepartment of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP)School of Biological Sciences University of Northern ColoradoDepartment of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP)University of Fortaleza (UNIFOR)Biochemistry and Molecular Biology DepartmentUniversidade Estadual Paulista (UNESP)University of Northern ColoradoJucá, Thiago LustosaRamos, Márcio VianaCilli, Eduardo Maffud [UNESP]Neto, Antônio Eufrásio VieiraMackessy, Stephen P.Monteiro-Moreira, Ana Cristina Oliveira2022-04-29T08:40:33Z2022-04-29T08:40:33Z2022-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1002/jmr.2957Journal of Molecular Recognition.1099-13520952-3499http://hdl.handle.net/11449/23051010.1002/jmr.29572-s2.0-85125772582Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Molecular Recognitioninfo:eu-repo/semantics/openAccess2022-04-29T08:40:33Zoai:repositorio.unesp.br:11449/230510Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T15:05:46.341103Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Insights on the inhibition properties of Jatromollistatin (a cyclic heptapeptide) against Crotalus adamanteus metalloendopeptidase using molecular docking analysis
title Insights on the inhibition properties of Jatromollistatin (a cyclic heptapeptide) against Crotalus adamanteus metalloendopeptidase using molecular docking analysis
spellingShingle Insights on the inhibition properties of Jatromollistatin (a cyclic heptapeptide) against Crotalus adamanteus metalloendopeptidase using molecular docking analysis
Jucá, Thiago Lustosa
latex
laticifers
orbitides
snake venom
solid phase extraction
title_short Insights on the inhibition properties of Jatromollistatin (a cyclic heptapeptide) against Crotalus adamanteus metalloendopeptidase using molecular docking analysis
title_full Insights on the inhibition properties of Jatromollistatin (a cyclic heptapeptide) against Crotalus adamanteus metalloendopeptidase using molecular docking analysis
title_fullStr Insights on the inhibition properties of Jatromollistatin (a cyclic heptapeptide) against Crotalus adamanteus metalloendopeptidase using molecular docking analysis
title_full_unstemmed Insights on the inhibition properties of Jatromollistatin (a cyclic heptapeptide) against Crotalus adamanteus metalloendopeptidase using molecular docking analysis
title_sort Insights on the inhibition properties of Jatromollistatin (a cyclic heptapeptide) against Crotalus adamanteus metalloendopeptidase using molecular docking analysis
author Jucá, Thiago Lustosa
author_facet Jucá, Thiago Lustosa
Ramos, Márcio Viana
Cilli, Eduardo Maffud [UNESP]
Neto, Antônio Eufrásio Vieira
Mackessy, Stephen P.
Monteiro-Moreira, Ana Cristina Oliveira
author_role author
author2 Ramos, Márcio Viana
Cilli, Eduardo Maffud [UNESP]
Neto, Antônio Eufrásio Vieira
Mackessy, Stephen P.
Monteiro-Moreira, Ana Cristina Oliveira
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv University of Fortaleza (UNIFOR)
Biochemistry and Molecular Biology Department
Universidade Estadual Paulista (UNESP)
University of Northern Colorado
dc.contributor.author.fl_str_mv Jucá, Thiago Lustosa
Ramos, Márcio Viana
Cilli, Eduardo Maffud [UNESP]
Neto, Antônio Eufrásio Vieira
Mackessy, Stephen P.
Monteiro-Moreira, Ana Cristina Oliveira
dc.subject.por.fl_str_mv latex
laticifers
orbitides
snake venom
solid phase extraction
topic latex
laticifers
orbitides
snake venom
solid phase extraction
description Jatropha mollissima is endemic to Brazil and is used for traditional medicinal purposes, including the treatment of snakebite. In this study, latex obtained from this plant was fractioned using reversed-phase chromatography, and the fractions were then screened for peptides. A 755 g/mol peptide was obtained, and MS/MS analyses indicated it had a cyclic sequence (Pro-Leu-Gly-Val-Leu-Leu-Tyr). This peptide sequence was present in the Jatropha genome database, and an identity value of 90.71%, an E-value of 0.0, and a score of 883 with NO-associated protein 1/chloroplastic/mitochondria of Jatropha curcas were obtained from the NCBI nonredundant protein sequence (nr) database. Molecular docking analyses performed with the peptide against a metalloendopeptidase belonging to Crotalus adamanteus snake venom suggested the cyclic peptide establishes favorable interactions with the catalytic site of the enzyme. Therefore, it could inhibit enzyme catalysis. This belief was corroborated by the formation of 6 hydrogen bonds with the linear form of the peptide. Tighter complexation of the cyclic form (41 kcal/mol more energetic) revealed better spatial blocking. The linear form outperformed the cyclic form in complexing the required energy, recruiting more catalytic residues (6/2), and in establishing more hydrogen bonds (6/3). However, cyclic folding provided a more significant spatial block within the catalytic site. The set of results suggests that the cycle peptide, here called Jatromollistatin, which was previously described as jatrophidin and pohlianin A in two other species of Jatropha, is a promising candidate to inhibit venom proteases. This belief is corroborated by the topical use of the latex for initial treatment of snakebites.
publishDate 2022
dc.date.none.fl_str_mv 2022-04-29T08:40:33Z
2022-04-29T08:40:33Z
2022-01-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1002/jmr.2957
Journal of Molecular Recognition.
1099-1352
0952-3499
http://hdl.handle.net/11449/230510
10.1002/jmr.2957
2-s2.0-85125772582
url http://dx.doi.org/10.1002/jmr.2957
http://hdl.handle.net/11449/230510
identifier_str_mv Journal of Molecular Recognition.
1099-1352
0952-3499
10.1002/jmr.2957
2-s2.0-85125772582
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Molecular Recognition
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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