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S(1)' and S(2)' Subsite Specificities of Human Plasma Kallikrein and Tissue Kallikrein 1 for the Hydrolysis of Peptides Derived from the Bradykinin Domain of Human Kininogen

Title: S(1)' and S(2)' Subsite Specificities of Human Plasma Kallikrein and Tissue Kallikrein 1 for the Hydrolysis of Peptides Derived from the Bradykinin Domain of Human Kininogen.
Name(s): Lima, Aurelio, author
Alves, Fabiana, author
Angelo, Pedro, author
Andrade, Douglas, author
Blaber, Sachiko, author
Blaber, Michael, author
Juliano, Luiz, author
Juliano, Maria, author
Type of Resource: text
Genre: text
Issuance: serial
Date Issued: 2008
Physical Form: computer
Physical Form: online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The S(1)' and S(2)' subsite specificities of human tissue kallikrein 1 (KLK1) and human plasma kallikrein (HPK) were examined with the peptide series Abz-GFSPFRXSRIQ-EDDnp and Abz-GFSPFRSXRIQ-EDDnp [X=natural amino acids or S(PO(3)H(2))]. KLK1 efficiently hydrolyzed most of the peptides except those containing negatively charged amino acids at P(1)' and P(2)' positions. Abz-GFSPFRSSRIQ-EDDnp, as in human kininogen, is the best substrate for KLK1 and exclusively cleaved the R-S bond. All other peptides were cleaved also at the F-R bond. The synthetic human kininogen segment Abz-MISLMKRPPGFSPFRS(390)S(391)RI-NH(2) was hydrolyzed by KLK1 first at R-S and then at M-K bonds, releasing Lys-bradykinin. In the S(390) and S(391) phosphorylated analogs, this order of hydrolysis was inverted due to the higher resistance of the R-S bond. Abz-MISLMKRPPG-FSPFRSS(PO(3)H(2))(391)RI-NH(2) was hydrolyzed by KLK1 at M-K and mainly at the F-R bond, releasing des-(Arg(9))-Lys-Bk which is a B1 receptor agonist. HPK cleaved all the peptides at R and showed restricted specificity for S in the S(1)' subsite, with lower specificity for the S(2)' subsite. Abz-MISLMKRPPGFSPFRSSRI-NH(2) was efficiently hydrolyzed by HPK under bradykinin release, while the analogs containing S(PO(3)H(2)) were poorly hydrolyzed. In conclusion, S(1)' and S(2)' subsite specificities of KLK1 and HPK showed peculiarities that were observed with substrates containing the amino acid sequence of human kininogen.
Identifier: FSU_migr_biomed_faculty_publications-0011 (IID)
Keywords: bradykinin, kinin, peptidase, peptides, phosphorylation, protease
Uncontrolled subjects: Amino Acid Sequence, Anthranilic Acids, Bradykinin, Fluorescence Resonance Energy Transfer, Humans, Hydrolysis, Kinetics, Kininogens, Kinins, Molecular Sequence Data, Peptides, Phosphorylation, Plasma Kallikrein, Recombinant Proteins, Substrate Specificity, Tissue Kallikreins
Note: Originally published in Biological Chemistry.
Citation: Lima, A.R., Alves, F.M., Angelo, P.F., Andrade, D., Blaber, S.I., Blaber, M., Juliano.L. and Juliano, M.A. (2008). S(1)' and S(2)' subsite specificities of human plasma kalikrein and tissue kallikrein 1 on the hydrolysis of peptides derived from bradykinin domain of human kininogen. Biological Chemistry 389, 1487-1494.
Subject(s): Biochemistry
Molecular biology
Developmental biology
Clinical biochemistry
Medical sciences
Persistent Link to This Record:
Owner Institution: FSU
Is Part of Series: Department of Biomedical Sciences Faculty Publications.
Is Part Of: Biological Chemistry.
Issue: 12, 389