cADP-ribose, which is produced by ecto-ADP-ribosyl cyclase of CD38 or bone marrow stromal cell antigen-1 (BST-1), is a key regulator of Ca2+-induced calcium release in an Ins(1,4,5)P3-independent manner. In the present study, we have identified a specific peptide inhibitor for ADP-ribosyl cyclase of BST-1. A 15-mer random peptide phage library was screened with a soluble form of BST-1 expressed in baculovirus-infected insect cells. After biopanning, two potent sequences reactive towards BST-1 were isolated. The two synthetic peptides corresponding to the identified sequences were shown to antagonize each other's ability to inhibit the binding of the two isolated phage to BST-1, suggesting that they bind at a common binding site on BST-1. One of the peptides (SNP-1) was shown to inhibit ADP-ribosyl cyclase activity of BST-1 in an uncompetitive manner with a Ki value of 180±40 nM (n = 3). SNP-1 also inhibited cyclic ADP-ribose hydrolase activity of BST-1 dose-dependently. Selected phage did not cross-react with a soluble form of CD38. SNP-1 did not show any inhibitory effect on ADP-ribosyl cyclase activity of CD38, and therefore this peptide inhibitor will be useful to serve as a starting tool for understanding the roles of these intriguing ecto-enzymes. This is the first report of a specific ADP-ribosyl cyclase inhibitor.
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February 1999
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Research Article|
January 25 1999
Novel peptide inhibitor of ecto-ADP-ribosyl cyclase of bone marrow stromal cell antigen-1 (BST-1/CD157) Available to Purchase
Atsushi SATO;
Atsushi SATO
*Department of Molecular Biology, Biomolecular Engineering Research Institute, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan
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Sumie YAMAMOTO;
Sumie YAMAMOTO
*Department of Molecular Biology, Biomolecular Engineering Research Institute, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan
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Katsuhiko ISHIHARA;
Katsuhiko ISHIHARA
†Department of Molecular Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Osaka 565-0871, Japan
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Toshio HIRANO;
Toshio HIRANO
†Department of Molecular Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Osaka 565-0871, Japan
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Hisato JINGAMI
Hisato JINGAMI
1
*Department of Molecular Biology, Biomolecular Engineering Research Institute, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan
1To whom correspondence should be addressed (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
August 17 1998
Revision Received:
October 15 1998
Accepted:
November 11 1998
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 337 (3): 491–496.
Article history
Received:
August 17 1998
Revision Received:
October 15 1998
Accepted:
November 11 1998
Citation
Atsushi SATO, Sumie YAMAMOTO, Katsuhiko ISHIHARA, Toshio HIRANO, Hisato JINGAMI; Novel peptide inhibitor of ecto-ADP-ribosyl cyclase of bone marrow stromal cell antigen-1 (BST-1/CD157). Biochem J 1 February 1999; 337 (3): 491–496. doi: https://doi.org/10.1042/bj3370491
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