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Substrate Specificity of Human Kallikreins 1 and 6 Determined by Phage Display

Title: Substrate Specificity of Human Kallikreins 1 and 6 Determined by Phage Display.
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Name(s): Li, Hai-Xin, author
Hwang, Bum-Yeol, author
Laxmikanthan, Gurunathan, 1979-, author
Blaber, Sachiko, author
Blaber, Michael, author
Golubkov, Pavel, author
Ren, Pengyu, author
Iverson, Brent, author
Georgiou, George, author
Type of Resource: text
Genre: Text
Issuance: serial
Date Issued: 2008
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The human tissue kallikrein (KLK) family contains 15 secreted serine proteases that are expressed in a wide range of tissues and have been implicated in different physiological functions and disease states. Of these, KLK1 has been shown to be involved in the regulation of multiple physiological processes such as blood pressure, smooth muscle contraction, and vascular cell growth. KLK6 is overexpressed in breast and ovarian cancer tissues and has been shown to cleave peptide derived from human myelin protein and Abeta amyloid peptide in vitro. Here we analyzed the substrate specificity of KLK1 and KLK6, by substrate phage display using a random octapeptide library. Consistent with earlier biochemical data, KLK1 was shown to exhibit both trypsin- and chymotrypsin-like selectivities with Tyr/Arg preferred at site P1, Ser/Arg strongly preferred at P1', and Phe/Leu at P2. KLK6 displayed trypsin-like activity, with the P1 position occupied only by Arg and a strong preference for Ser in P1'. Docking simulations of consensus peptide provide information on the identity of the enzyme residues that are responsible for substrate binding. Bioinformatic analysis suggested several putative KLK6 protein substrates, such as ionotropic glutamate receptor (GluR) and synphilin.
Identifier: FSU_migr_biomed_faculty_publications-0006 (IID)
Keywords: human kallikrein, phage display, substrate specificity, molecular modeling
Uncontrolled subjects: Amino Acid Sequence, Binding Sites, Humans, Kallikreins, Kinetics, Models, Molecular, Oligopeptides, Peptide Library, Substrate Specificity, Tissue Kallikreins
Note: Originally published in Protein Science
Citation: Li, H.-X., Hwang, B.-Y., Laxmikanthan, G., Blaber, S.I., Blaber, M., Golubkov, P.A., Ren, P., Iverson, B.L. and Georgiou, G. (2008). Substrate specificity of human kallikreins 1 and 6 determined by phage display. Protein Science 17, 664-672.
Subject(s): Biochemistry
Biophysics
Molecular biology
Cytology
Developmental biology
Clinical biochemistry
Medical sciences
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_migr_biomed_faculty_publications-0006
Owner Institution: FSU
Is Part of Series: Department of Biomedical Sciences Faculty Publications.
Is Part Of: Protein Science : A Publication of the Protein Society.
Issue: 4, 17

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Li, H. -X., Hwang, B. -Y., Laxmikanthan, G., Blaber, S., Blaber, M., Golubkov, P., … Georgiou, G. (2008). Substrate Specificity of Human Kallikreins 1 and 6 Determined by Phage Display. Protein Science . Retrieved from http://purl.flvc.org/fsu/fd/FSU_migr_biomed_faculty_publications-0006