Epitope mapping of the domains of human angiotensin converting enzyme

• Published in: Biochimica et biophysica acta Vol. 1760; no. 6; pp. 959 - 965
• Main Authors: Kugaevskaya, Elena V., Kolesanova, Ekaterina F., Kozin, Sergey A., Veselovsky, Alexander V., Dedinsky, Ilya R., Elisseeva, Yulia E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-06-2006
• Subjects: ACE; Amino Acid Sequence; Animals; Antigen determinants; Domains; Epitope Mapping; Epitopes - chemistry; Humans; Male; Models, Molecular; Molecular Sequence Data; Peptidyl-Dipeptidase A - chemistry; Peptidyl-Dipeptidase A - immunology; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Alignment; Structure; Testis - enzymology; Domains; ACE; Structure; Antigen determinants
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2006.02.011

Somatic angiotensin converting enzyme (sACE), contains in its single chain two homologous domains (called N- and C-domains), each bearing a functional zinc-dependent active site. The present study aims to define the differences between two sACE domains and to localize experimentally revealed antigenic determinants (B-epitopes) in the recently determined three-dimensional structure of testicular tACE. The predicted linear antigenic determinants of human sACE were determined by peptide scanning (“PEPSCAN”) approach. Essential difference was demonstrated between locations of the epitopes in the N- and C-domains. Comparison of arrangement of epitopes in the human domains with the corresponding sequences of some mammalian sACEs enabled to classify the revealed antigenic determinants as variable or conserved areas. The location of antigenic determinants with respect to various structural elements and to functionally important sites of the human sACE C-domain was estimated. The majority of antigenic sites of the C-domain were located at the irregular elements and at the boundaries of secondary structure elements. The data show structural differences between the sACE domains. The experimentally revealed antigenic determinants were in agreement with the recently determined crystal tACE structure. New potential applications are open to successfully produce mono-specific and group-specific antipeptide antibodies.