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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Online
ISSN
1437-4315
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Volume 390, Issue 9 (Sep 2009)

Issues

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

Carlos Eduardo L. Cunha
  • Department of Biophysics, Federal University of São Paulo, Rua 3 de Maio 100, 04044-020 São Paulo, SP, Brazil
  • These authors contributed equally to this work.
/ Helena de Fátima Magliarelli
  • Department of Biophysics, Federal University of São Paulo, Rua 3 de Maio 100, 04044-020 São Paulo, SP, Brazil
  • These authors contributed equally to this work.
/ Thaysa Paschoalin
  • Department of Biophysics, Federal University of São Paulo, Rua 3 de Maio 100, 04044-020 São Paulo, SP, Brazil
  • Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, Rua Botucatu 862, 8º andar, 04023-062 São Paulo, SP, Brazil
/ Aloysius T. Nchinda
  • Division of Medical Biochemistry, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, Cape Town, South Africa
/ Jackson C. Lima
  • Department of Information Technology in Health, Federal University of São Paulo, Rua Botucatu 862, 04023-062 São Paulo, SP, Brazil
/ Maria A. Juliano
  • Department of Biophysics, Federal University of São Paulo, Rua 3 de Maio 100, 04044-020 São Paulo, SP, Brazil
/ Paulo B. Paiva
  • Department of Information Technology in Health, Federal University of São Paulo, Rua Botucatu 862, 04023-062 São Paulo, SP, Brazil
/ Edward D. Sturrock
  • Division of Medical Biochemistry, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, Cape Town, South Africa
/ Luiz R. Travassos
  • Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, Rua Botucatu 862, 8º andar, 04023-062 São Paulo, SP, Brazil
/ Adriana K. Carmona
  • Department of Biophysics, Federal University of São Paulo, Rua 3 de Maio 100, 04044-020 São Paulo, SP, Brazil
Published Online: 2009-06-27 | DOI: https://doi.org/10.1515/BC.2009.105

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 S3 to S1′ 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 μm) and with two C-domain-selective ACE inhibitors, 5-S-5-benzamido-4-oxo-6-phenylhexanoyl-L-tryptophan (kAW; K i=22.0 μm) 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.

Keywords: angiotensin I-converting enzyme; dipeptidyl carboxypeptidase; inhibitors; molecular modeling; phylogeny; specificity studies

About the article

Corresponding author


Received: 2009-02-19

Accepted: 2009-05-13

Published Online: 2009-06-27

Published in Print: 2009-09-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2009.105. Export Citation

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