Heparin modulation of human plasma kallikrein on different substrates and inhibitors

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dc.contributor.authorGozzo, Andrezza Justino [UNIFESP]
dc.contributor.authorNunes, Viviane A. [UNIFESP]
dc.contributor.authorCruz-Silva, Ilana [UNIFESP]
dc.contributor.authorCarmona, Adriana K. [UNIFESP]
dc.contributor.authorNader, Helena Bonciani [UNIFESP]
dc.contributor.authorFaljoni-Alario, Adelaide
dc.contributor.authorSampaio, Misako U. [UNIFESP]
dc.contributor.authorAraujo, Mariana S. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2016-01-24T12:41:23Z
dc.date.available2016-01-24T12:41:23Z
dc.date.issued2006-08-01
dc.description.abstractThe interplay of different proteases and glycosaminoglycans is able to modulate the activity of the enzymes and to affect their structures. Human plasma kallikrein ( huPK) is a proteolytic enzyme involved in intrinsic blood clotting, the kallikrein-kinin system and fibrinolysis. We investigated the effect of heparin on the action, inhibition and secondary structure of huPK. the catalytic efficiency for the hydrolysis of substrates by huPK was determined by Michaelis-Menten kinetic plots: 5.12 x 10(4) M-1 S-1 for acetyl-Phe-Arg-p-nitroanilide, 1.40 x 10(5) M-1 S-1 for H-D-ProPhe-Arg-p-nitroanilide, 2.25 x 10(4) M-1 S-1 for Abz-Gly-Phe-Ser-Pro-Phe-Arg-Ser-Ser-Arg-Gln-EDDnp, 4.24 x 10(2) M-1 S-1 for factor XII and 5.58 x 10(2) M-1 S-1 for plasminogen. Heparin reduced the hydrolysis of synthetic substrates ( by 2.0-fold), but enhanced factor XII and plasminogen hydrolysis ( 7.7- and 1.4-fold, respectively). the second-order rate constants for inhibition of huPK by antithrombin and C1-inhibitor were 2.40 x 10(2) M-1 S-1 and 1.70 x 10(4) M-1 S-1, respectively. Heparin improved the inhibition of huPK by these inhibitors ( 3.4- and 1.4-fold). Despite the fact that huPK was able to bind to a heparin-Sepharose matrix, its secondary structure was not modified by heparin, as monitored by circular dichroism. These actions may have a function in the control or maintenance of some pathophysiological processes in which huPK participates.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Dept Bioquim, Inst Quim, BR-05508900 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent1129-1138
dc.identifierhttp://dx.doi.org/10.1515/BC.2006.139
dc.identifier.citationBiological Chemistry. Berlin: Walter de Gruyter & Co, v. 387, n. 8, p. 1129-1138, 2006.
dc.identifier.doi10.1515/BC.2006.139
dc.identifier.issn1431-6730
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/29086
dc.identifier.wosWOS:000240351400016
dc.language.isoeng
dc.publisherWalter de Gruyter & Co
dc.relation.ispartofBiological Chemistry
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectantithrombinen
dc.subjectC1-inhibitoren
dc.subjectfactor XIIen
dc.subjectglycosaminoglycansen
dc.subjectplasminogenen
dc.subjectsynthetic substratesen
dc.titleHeparin modulation of human plasma kallikrein on different substrates and inhibitorsen
dc.typeinfo:eu-repo/semantics/article
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