Catalytic properties of recombinant dipeptidyl carboxypeptidase from Escherichia coli: a comparative study with angiotensin I-converting enzyme

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dc.contributor.author Cunha, Carlos Eduardo L. [UNIFESP]
dc.contributor.author Magliarelli, Helena de Fatima [UNIFESP]
dc.contributor.author Paschoalin, Thaysa [UNIFESP]
dc.contributor.author Nchinda, Aloysius T.
dc.contributor.author Lima, Jackson C. [UNIFESP]
dc.contributor.author Juliano, Maria A. [UNIFESP]
dc.contributor.author Paiva, Paulo B. [UNIFESP]
dc.contributor.author Sturrock, Edward D.
dc.contributor.author Travassos, Luiz R. [UNIFESP]
dc.contributor.author Carmona, Adriana K. [UNIFESP]
dc.date.accessioned 2016-01-24T13:58:44Z
dc.date.available 2016-01-24T13:58:44Z
dc.date.issued 2009-09-01
dc.identifier http://dx.doi.org/10.1515/BC.2009.105
dc.identifier.citation Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 390, n. 9, p. 931-940, 2009.
dc.identifier.issn 1431-6730
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/31807
dc.description.abstract Dipeptidyl carboxypeptidase from Escherichia coli (EcDcp) is a zinc metallopeptidase with catalytic properties closely resembling those of angiotensin I-converting enzyme (ACE). However, EcDcp and ACE are classified in different enzyme families (M3 and M2, respectively) due to differences in their primary sequences. We cloned and expressed EcDcp and studied in detail the enzyme's S(3) to S(1)' substrate specificity using positional-scanning synthetic combinatorial (PS-SC) libraries of fluorescence resonance energy transfer (FRET) peptides. These peptides contain ortho-aminobenzoic acid (Abz) and 2,4-dinitrophenyl (Dnp) as donor/acceptor pair. in addition, using FRET substrates developed for ACE [Abz-FRK(Dnp)P-OH, Abz-SDK(Dnp)P-OH and Abz-LFK(Dnp)-OH] as well as natural ACE substrates (angiotensin I, bradykinin, and Ac-SDKP-OH), we show that EcDcp has catalytic properties very similar to human testis ACE. EcDcp inhibition studies were performed with the ACE inhibitors captopril (K(i) = 3 nM) and lisinopril (K(i) = 4.4 mu M) and with two C-domain-selective ACE inhibitors, 5-S-5-benzamido-4-oxo-6-phenylhexanoyl-L-tryptophan (kAW; K(i) = 22.0 mu M) and lisinopril-Trp (K(i) = 0.8 nM). Molecular modeling was used to provide the basis for the differences found in the inhibitors potency. the phylogenetic relationship of EcDcp and related enzymes belonging to the M3 and M2 families was also investigated and the results corroborate the distinct origins of EcDcp and ACE. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorship Wellcome Trust, UK
dc.description.sponsorship National Research Foundation
dc.format.extent 931-940
dc.language.iso eng
dc.publisher Walter de Gruyter & Co
dc.relation.ispartof Biological Chemistry
dc.rights Acesso restrito
dc.subject angiotensin I-converting enzyme en
dc.subject dipeptidyl carboxypeptidase en
dc.subject inhibitors en
dc.subject molecular modeling en
dc.subject phylogeny en
dc.subject specificity studies en
dc.title Catalytic properties of recombinant dipeptidyl carboxypeptidase from Escherichia coli: a comparative study with angiotensin I-converting enzyme en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Univ Cape Town
dc.description.affiliation Universidade Federal de São Paulo, Dept Biophys, BR-04044020 São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.affiliation Univ Cape Town, Div Med Biochem, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa
dc.description.affiliation Universidade Federal de São Paulo, Dept Informat Technol Hlth, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Biophys, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Informat Technol Hlth, BR-04023062 São Paulo, Brazil
dc.identifier.doi 10.1515/BC.2009.105
dc.description.source Web of Science
dc.identifier.wos WOS:000269485600012



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