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

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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; Hollingsworth, K; Vihinen, M; Bridon, D; Qiu, X; Rapp, J; Dowell, B; Lovgren, T; Pettersson, K; Lilja, Hans.

In: Protein Science, Vol. 7, No. 2, 1998, p. 259-269.

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Piironen, T ; Villoutreix, Bruno O ; Becker, Charlotte ; Hollingsworth, K ; Vihinen, M ; Bridon, D ; Qiu, X ; Rapp, J ; Dowell, B ; Lovgren, T ; Pettersson, K ; Lilja, Hans. / Determination and analysis of antigenic epitopes of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2) using synthetic peptides and computer modeling. In: Protein Science. 1998 ; Vol. 7, No. 2. pp. 259-269.

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TY - JOUR

T1 - Determination and analysis of antigenic epitopes of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2) using synthetic peptides and computer modeling

AU - Piironen, T

AU - Villoutreix, Bruno O

AU - Becker, Charlotte

AU - Hollingsworth, K

AU - Vihinen, M

AU - Bridon, D

AU - Qiu, X

AU - Rapp, J

AU - Dowell, B

AU - Lovgren, T

AU - Pettersson, K

AU - Lilja, Hans

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

KW - alpha- 1 -antichymotrypsin

KW - computer-aided molecular modeling

KW - human glandular kallikrein

KW - monoclonalantibodies

KW - peptide mapping

KW - prostate cancer

KW - prostate specific antigen

KW - serine protease

KW - serpin

U2 - 10.1002/pro.5560070205

DO - 10.1002/pro.5560070205

M3 - Article

VL - 7

SP - 259

EP - 269

JO - Protein Science

JF - Protein Science

SN - 1469-896X

IS - 2

ER -