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Determination and analysis of antigenic epitopes of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2) using synthetic peptides and computer modeling

Piironen, T; Villoutreix, Bruno O; Becker, Charlotte LU ; Hollingsworth, K; Vihinen, M; Bridon, D; Qiu, X; Rapp, J; Dowell, B and Lovgren, T, et al. (1998) In Protein Science 7(2). p.259-269
Abstract
Prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2), produced essentially by the prostate gland, are 237-amino acid monomeric proteins, with 79% identity in primary structure. Twenty-five anti-PSA monoclonal antibodies (Mabs) were studied for binding to a large array of synthetic linear peptides selected from computer models of PSA and hK2, as well as to biotinylated peptides covering the entire PSA sequence. Sixteen of the Mabs were bound to linear peptides forming four independent binding regions (I-IV). Binding region I was localized to amino acid residues 1-13 (identical sequence for PSA and hK2), II (a and b) was localized to residues 53-64, III (a and b) was localized to residues 80-91 (= kallikrein loop), and IV... (More)
Prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2), produced essentially by the prostate gland, are 237-amino acid monomeric proteins, with 79% identity in primary structure. Twenty-five anti-PSA monoclonal antibodies (Mabs) were studied for binding to a large array of synthetic linear peptides selected from computer models of PSA and hK2, as well as to biotinylated peptides covering the entire PSA sequence. Sixteen of the Mabs were bound to linear peptides forming four independent binding regions (I-IV). Binding region I was localized to amino acid residues 1-13 (identical sequence for PSA and hK2), II (a and b) was localized to residues 53-64, III (a and b) was localized to residues 80-91 (= kallikrein loop), and IV was localized to residues 151-164. Mabs binding to regions I and IIa were reactive with free PSA, PSA-ACT complex, and with hK2; Mabs binding to regions IIb, IIIa, and IV were reactive with free PSA and PSA-ACT complex, but unreactive with hK2; Mabs binding to region IIIb detected free PSA only. All Mabs tested (n = 7) specific for free PSA reacted with kallikrein loop (binding region IIIb). The presence of Mabs interacting with binding region I did not inhibit the catalytic activity of PSA, whereas Mabs interacting with other binding regions inhibited the catalysis. Theoretical model structures of PSA, hK2, and the PSA-ACT complex were combined with the presented data to suggest an overall orientation of PSA with regard to ACT. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
keywords
alpha- 1 -antichymotrypsin, computer-aided molecular modeling, human glandular kallikrein, monoclonal antibodies, peptide mapping, prostate cancer, prostate specific antigen, serine protease, serpin
in
Protein Science
volume
7
issue
2
pages
259 - 269
publisher
The Protein Society
external identifiers
  • pmid:9521101
  • wos:000072056400005
  • scopus:0031913879
ISSN
1469-896X
language
English
LU publication?
no
id
f2f33b22-e135-4f74-a9ce-35adf8ec69c2 (old id 1113469)
alternative location
http://protsci.highwire.org/cgi/reprint/7/2/259
date added to LUP
2008-07-15 10:37:51
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2017-01-01 04:58:41
@article{f2f33b22-e135-4f74-a9ce-35adf8ec69c2,
  abstract     = {Prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2), produced essentially by the prostate gland, are 237-amino acid monomeric proteins, with 79% identity in primary structure. Twenty-five anti-PSA monoclonal antibodies (Mabs) were studied for binding to a large array of synthetic linear peptides selected from computer models of PSA and hK2, as well as to biotinylated peptides covering the entire PSA sequence. Sixteen of the Mabs were bound to linear peptides forming four independent binding regions (I-IV). Binding region I was localized to amino acid residues 1-13 (identical sequence for PSA and hK2), II (a and b) was localized to residues 53-64, III (a and b) was localized to residues 80-91 (= kallikrein loop), and IV was localized to residues 151-164. Mabs binding to regions I and IIa were reactive with free PSA, PSA-ACT complex, and with hK2; Mabs binding to regions IIb, IIIa, and IV were reactive with free PSA and PSA-ACT complex, but unreactive with hK2; Mabs binding to region IIIb detected free PSA only. All Mabs tested (n = 7) specific for free PSA reacted with kallikrein loop (binding region IIIb). The presence of Mabs interacting with binding region I did not inhibit the catalytic activity of PSA, whereas Mabs interacting with other binding regions inhibited the catalysis. Theoretical model structures of PSA, hK2, and the PSA-ACT complex were combined with the presented data to suggest an overall orientation of PSA with regard to ACT.},
  author       = {Piironen, T and Villoutreix, Bruno O and Becker, Charlotte and Hollingsworth, K and Vihinen, M and Bridon, D and Qiu, X and Rapp, J and Dowell, B and Lovgren, T and Pettersson, K and Lilja, Hans},
  issn         = {1469-896X},
  keyword      = {alpha- 1 -antichymotrypsin,computer-aided molecular modeling,human glandular kallikrein,monoclonal
antibodies,peptide mapping,prostate cancer,prostate specific antigen,serine protease,serpin},
  language     = {eng},
  number       = {2},
  pages        = {259--269},
  publisher    = {The Protein Society},
  series       = {Protein Science},
  title        = {Determination and analysis of antigenic epitopes of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2) using synthetic peptides and computer modeling},
  volume       = {7},
  year         = {1998},
}