Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activities
Autor(a) principal: | |
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Data de Publicação: | 2003 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1110/ps.03102403 http://hdl.handle.net/11449/21996 |
Resumo: | BaP1 is a 22.7-kD P-I-type zinc-dependent metalloproteinase isolated from the venom of the snake Bothrops asper, a medically relevant species in Central America. This enzyme exerts multiple tissue-damaging activities, including hemorrhage, myonecrosis, dermonecrosis, blistering, and edema. BaP1 is a single chain of 202 amino acids that shows highest sequence identity with metalloproteinases isolated front the venoms of snakes of the subfamily Crotalinae. It has six Cys residues involved in three disulfide bridges (Cys 117-Cys 197, Cys 159-Cys 181, Cys 157-Cys 164). It has the consensus sequence H(142)E(143)XXH(146)XXGXXH(152), as well as the sequence C164I165M166, which characterize the metzincin superfamily of metalloproteinases. The active-site cleft separates a major subdomain (residues 1-152), comprising four a-helices and a five-stranded beta-sheet, from the minor subdomain, which is formed by a single a-helix and several loops. The catalytic zinc ion is coordinated by the N-epsilon2 nitrogen atoms of His 142, His 146, and His 152, in addition to a solvent water molecule, which in turn is bound to Glu 143. Several conserved residues contribute to the formation of the hydrophobic pocket, and Met 166 serves as a hydrophobic base for the active-site groups. Sequence and structural comparisons of hemorrhagic and nonhemorrhagic P-I metalloproteinases from snake venoms revealed differences in several regions. In particular, the loop comprising residues 153 to 176 has marked structural differences between metalloproteinases with very different hemorrhagic activities. Because this region lies in close proximity to the active-site microenvironment, it may influence the interaction of these enzymes with physiologically relevant substrates in the extracellular matrix. |
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Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activitiessnake venomzinc-dependent metalloproteinasesmetzincinshemorrhagic toxinsamino acid sequenceCrystal structureBaP1 is a 22.7-kD P-I-type zinc-dependent metalloproteinase isolated from the venom of the snake Bothrops asper, a medically relevant species in Central America. This enzyme exerts multiple tissue-damaging activities, including hemorrhage, myonecrosis, dermonecrosis, blistering, and edema. BaP1 is a single chain of 202 amino acids that shows highest sequence identity with metalloproteinases isolated front the venoms of snakes of the subfamily Crotalinae. It has six Cys residues involved in three disulfide bridges (Cys 117-Cys 197, Cys 159-Cys 181, Cys 157-Cys 164). It has the consensus sequence H(142)E(143)XXH(146)XXGXXH(152), as well as the sequence C164I165M166, which characterize the metzincin superfamily of metalloproteinases. The active-site cleft separates a major subdomain (residues 1-152), comprising four a-helices and a five-stranded beta-sheet, from the minor subdomain, which is formed by a single a-helix and several loops. The catalytic zinc ion is coordinated by the N-epsilon2 nitrogen atoms of His 142, His 146, and His 152, in addition to a solvent water molecule, which in turn is bound to Glu 143. Several conserved residues contribute to the formation of the hydrophobic pocket, and Met 166 serves as a hydrophobic base for the active-site groups. Sequence and structural comparisons of hemorrhagic and nonhemorrhagic P-I metalloproteinases from snake venoms revealed differences in several regions. In particular, the loop comprising residues 153 to 176 has marked structural differences between metalloproteinases with very different hemorrhagic activities. Because this region lies in close proximity to the active-site microenvironment, it may influence the interaction of these enzymes with physiologically relevant substrates in the extracellular matrix.Univ Costa Rica, Fac Microbiol, Inst Clodomiro Picado, San Jose, Costa RicaUniv Costa Rica, Escuela Med, Dept Bioquim, San Jose, Costa RicaUniv Liverpool, Royal Liverpool Univ Hosp, Dept Haematol, Liverpool, Merseyside, EnglandUniv Liverpool, Liverpool Sch Trop Med, Venom Res Unit, Liverpool L3 5QA, Merseyside, EnglandFiocruz MS, Dept Fisiol & Farmacodinam, BR-21045900 Rio de Janeiro, BrazilUniv Virginia, Hlth Sci Ctr, Dept Microbiol, Charlottesville, VA 22908 USAUNESP, IBILCE, Dept Phys, BR-15054000 Sao Jose do Rio Preto, BrazilUNESP, IBILCE, Dept Phys, BR-15054000 Sao Jose do Rio Preto, BrazilCold Spring Harbor Lab Press, Publications DeptUniv Costa RicaUniv LiverpoolFiocruz MSUniversity of Virginia (UVA)Universidade Estadual Paulista (Unesp)Watanabe, L.Shannon, J. D.Valente, R. H.Rucavado, A.Alape-Giron, A.Kamiguti, A. S.Theakston, RDGFox, J. W.Gutierrez, J. M.Arni, R. K.2014-05-20T14:02:24Z2014-05-20T14:02:24Z2003-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2273-2281application/pdfhttp://dx.doi.org/10.1110/ps.03102403Protein Science. Woodbury: Cold Spring Harbor Lab Press, Publications Dept, v. 12, n. 10, p. 2273-2281, 2003.0961-8368http://hdl.handle.net/11449/2199610.1110/ps.03102403WOS:000185425500016WOS000185425500016.pdf91625089789458870000-0003-2460-1145Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengProtein Science2.4101,652info:eu-repo/semantics/openAccess2024-01-15T06:20:59Zoai:repositorio.unesp.br:11449/21996Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T23:03:01.036828Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activities |
title |
Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activities |
spellingShingle |
Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activities Watanabe, L. snake venom zinc-dependent metalloproteinases metzincins hemorrhagic toxins amino acid sequence Crystal structure |
title_short |
Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activities |
title_full |
Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activities |
title_fullStr |
Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activities |
title_full_unstemmed |
Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activities |
title_sort |
Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activities |
author |
Watanabe, L. |
author_facet |
Watanabe, L. Shannon, J. D. Valente, R. H. Rucavado, A. Alape-Giron, A. Kamiguti, A. S. Theakston, RDG Fox, J. W. Gutierrez, J. M. Arni, R. K. |
author_role |
author |
author2 |
Shannon, J. D. Valente, R. H. Rucavado, A. Alape-Giron, A. Kamiguti, A. S. Theakston, RDG Fox, J. W. Gutierrez, J. M. Arni, R. K. |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Univ Costa Rica Univ Liverpool Fiocruz MS University of Virginia (UVA) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Watanabe, L. Shannon, J. D. Valente, R. H. Rucavado, A. Alape-Giron, A. Kamiguti, A. S. Theakston, RDG Fox, J. W. Gutierrez, J. M. Arni, R. K. |
dc.subject.por.fl_str_mv |
snake venom zinc-dependent metalloproteinases metzincins hemorrhagic toxins amino acid sequence Crystal structure |
topic |
snake venom zinc-dependent metalloproteinases metzincins hemorrhagic toxins amino acid sequence Crystal structure |
description |
BaP1 is a 22.7-kD P-I-type zinc-dependent metalloproteinase isolated from the venom of the snake Bothrops asper, a medically relevant species in Central America. This enzyme exerts multiple tissue-damaging activities, including hemorrhage, myonecrosis, dermonecrosis, blistering, and edema. BaP1 is a single chain of 202 amino acids that shows highest sequence identity with metalloproteinases isolated front the venoms of snakes of the subfamily Crotalinae. It has six Cys residues involved in three disulfide bridges (Cys 117-Cys 197, Cys 159-Cys 181, Cys 157-Cys 164). It has the consensus sequence H(142)E(143)XXH(146)XXGXXH(152), as well as the sequence C164I165M166, which characterize the metzincin superfamily of metalloproteinases. The active-site cleft separates a major subdomain (residues 1-152), comprising four a-helices and a five-stranded beta-sheet, from the minor subdomain, which is formed by a single a-helix and several loops. The catalytic zinc ion is coordinated by the N-epsilon2 nitrogen atoms of His 142, His 146, and His 152, in addition to a solvent water molecule, which in turn is bound to Glu 143. Several conserved residues contribute to the formation of the hydrophobic pocket, and Met 166 serves as a hydrophobic base for the active-site groups. Sequence and structural comparisons of hemorrhagic and nonhemorrhagic P-I metalloproteinases from snake venoms revealed differences in several regions. In particular, the loop comprising residues 153 to 176 has marked structural differences between metalloproteinases with very different hemorrhagic activities. Because this region lies in close proximity to the active-site microenvironment, it may influence the interaction of these enzymes with physiologically relevant substrates in the extracellular matrix. |
publishDate |
2003 |
dc.date.none.fl_str_mv |
2003-10-01 2014-05-20T14:02:24Z 2014-05-20T14:02:24Z |
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/10.1110/ps.03102403 Protein Science. Woodbury: Cold Spring Harbor Lab Press, Publications Dept, v. 12, n. 10, p. 2273-2281, 2003. 0961-8368 http://hdl.handle.net/11449/21996 10.1110/ps.03102403 WOS:000185425500016 WOS000185425500016.pdf 9162508978945887 0000-0003-2460-1145 |
url |
http://dx.doi.org/10.1110/ps.03102403 http://hdl.handle.net/11449/21996 |
identifier_str_mv |
Protein Science. Woodbury: Cold Spring Harbor Lab Press, Publications Dept, v. 12, n. 10, p. 2273-2281, 2003. 0961-8368 10.1110/ps.03102403 WOS:000185425500016 WOS000185425500016.pdf 9162508978945887 0000-0003-2460-1145 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Protein Science 2.410 1,652 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
2273-2281 application/pdf |
dc.publisher.none.fl_str_mv |
Cold Spring Harbor Lab Press, Publications Dept |
publisher.none.fl_str_mv |
Cold Spring Harbor Lab Press, Publications Dept |
dc.source.none.fl_str_mv |
Web of Science 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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1808129484671418368 |