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dc.contributor.author
Caramelo, Julio Javier
dc.contributor.author
Florin-Christensen, Jorge
dc.contributor.author
Jacobsen, Monica Ofelia
dc.contributor.author
Delfino, Jose Maria
dc.date.available
2019-03-15T19:28:32Z
dc.date.issued
2000-03
dc.identifier.citation
Caramelo, Julio Javier; Florin-Christensen, Jorge; Jacobsen, Monica Ofelia; Delfino, Jose Maria; Mapping the catalytic pocket of phospholipases A2 and C using a novel set of phosphatidylcholines; Portland Press; Biochemical Journal; 346; 3; 3-2000; 679-690
dc.identifier.issn
0264-6021
dc.identifier.uri
http://hdl.handle.net/11336/71778
dc.description.abstract
A set of radioiodinatable phosphatidylcholines (PCs) derivatized with the Bolton-Hunter reagent (BHPCs) was synthesized to probe the substrate recognition and activity of phospholipases. A common feature of this series is the presence of a bulky 4-hydroxyphenyl group at the end of the fatty acyl chain attached to position sn-2. The distance between the end group and the glycerol backbone was varied by changing the length of the intervening fatty acyl chain (3-25 atoms). Except for the shortest, this chain includes at least one amide linkage. The usefulness of this series of substrates as a molecular ruler was tested by measuring the hydrolytic activities of Naja naja naja phospholipase A(2) (PLA(2)) and Bacillus cereus phospholipase C (PLC) in Triton X-100 micelles. The activity of PLA(2) proved to be highly dependent on the length of the fatty acyl chain linker, the shorter compounds (3-10 atoms) being very poor substrates. In contrast, the PLC activity profile exhibited much less discrimination. In both cases, PCs with 16-21 atom chains at position sn-2 yielded optimal activity. We interpret these findings in terms of fatty acyl chain length-related steric hindrance caused by the terminal aromatic group, affecting the activity of PLA(2) and, to a smaller extent, that of PLC. This notion agrees with the more extended recognition of aliphatic chains inside the narrow channel leading to the catalytic site in the former case. Molecular models of these substrates bound to PLA(2) were built on the basis of the crystallographic structure of Naja naja atra PLA(2) complexed with a phospholipid analogue. Docking of these substrates necessarily requires the intrusion of the bulky 4-hydroxyphenyl group inside the binding pocket and also the failure of the amide group to form hydrogen bonds inside the hydrophobic substrate channel.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Portland Press
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Phospholipases
dc.subject
Radiolabeled Phospholipids
dc.subject
Fatty Acid Chain Length
dc.subject
Substrate Recognition
dc.subject.classification
Otras Ciencias Biológicas
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Mapping the catalytic pocket of phospholipases A2 and C using a novel set of phosphatidylcholines
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-03-14T14:22:02Z
dc.journal.volume
346
dc.journal.number
3
dc.journal.pagination
679-690
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Caramelo, Julio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
dc.description.fil
Fil: Florin-Christensen, Jorge. Washington State University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Jacobsen, Monica Ofelia. Washington State University; Estados Unidos
dc.description.fil
Fil: Delfino, Jose Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
dc.journal.title
Biochemical Journal
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.biochemj.org/content/346/3/679.long
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220900/
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1042/bj3460679


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