Russian Journal of Bioorganic Chemistry

, Volume 34, Issue 3, pp 323–328 | Cite as

Characteristics of monoclonal antibody binding with the C domain of human angiotensin converting enzyme

  • I. A. Naperova
  • I. V. Balyasnikova
  • M. N. Petrov
  • A. V. Vakhitova
  • V. V. Evdokimov
  • S. M. Danilov
  • O. A. Kost
Article
  • 33 Downloads

Abstract

Binding of a panel of eight monoclonal antibodies (mAbs) with the C domain of angiotensin converting enzyme (ACE) to human testicular ACE (tACE) (corresponding to the C domain of the somatic enzyme) was studied, and the inhibition of the enzyme by the mAb 4A3 was found. The dissociation constants of complexes of two mAbs, 1B8 and 2H9, with tACE were 2.3 ± 0.4 and 2.5 ± 0.4 nM, respectively, for recombinant tACE and 4.7 ± 0.5 and 1.6 ± 0.3 nM for spermatozoid tACE. Competition parameters of mAb binding with tACE were obtained and analyzed. As a result, the eight mAbs were divided into three groups, whose binding epitopes did not overlap: (1) 1E10, 2B11, 2H9, 3F11, and 4E3; (2) 1B8 and 3F10; and (3) 1B3. A diagram demonstrating mAb competitive binding with tACE was proposed. Comparative analysis of mAb binding to human and chimpanzee ACE was carried out, which resulted in revealing of two amino acid residues, Lys677 and Pro730, responsible for binding of three antibodies, 1E10, 1B8, and 3F10. It was found by mutation of Asp616 located close to Lys677 for Leu that the mAb binding epitope 1E10 contains Asp616 and Lys677, whereas mAbs 1B8 and 3F10 contain Pro730.

Key words

angiotensin converting enzyme C domain monoclonal antibodies 

Abbreviations

ACE

angiotensin converting enzyme

tACE

testicular ACE

mAb

monoclonal antibody

ELISA

enzyme-linked immunosorbent assay

Hip

hippuryl

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Copyright information

© MAIK Nauka 2008

Authors and Affiliations

  • I. A. Naperova
    • 1
  • I. V. Balyasnikova
    • 2
  • M. N. Petrov
    • 1
  • A. V. Vakhitova
    • 1
  • V. V. Evdokimov
    • 3
  • S. M. Danilov
    • 2
  • O. A. Kost
    • 1
  1. 1.Faculty of ChemistryMoscow State UniversityVorob’evy gory, MoscowRussia
  2. 2.Faculty of AnesthesiologyIllinois UniversityUrbana, ILUSA
  3. 3.Research Institute of UrologyRosmedtekhnology, MoscowUSA

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