HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 275, Issue 20, 15572-15577, May 19, 2000

This Article Full Text Full Text (PDF) All Versions of this Article: 275/20/15572    most recent M001406200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lenarcic, B. Articles by Moczydlowski, E. Search for Related Content PubMed PubMed Citation Articles by Lenarcic, B. Articles by Moczydlowski, E. Social Bookmarking                      What's this?

J Biol Chem, Vol. 275, Issue 20, 15572-15577, May 19, 2000

Saxiphilin, a Saxitoxin-binding Protein with Two Thyroglobulin Type 1 Domains, Is an Inhibitor of Papain-like Cysteine Proteinases^*

Brigita Lenari^§, Gomathi Krishnan^¶, Renata Borukhovich^¶, Brian Ruck^¶, Vito Turk, and Edward Moczydlowski^¶

From the Departments of  Biochemistry and Molecular Biology, J. Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia and the Departments of ^¶ Pharmacology and  Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8066

The type 1 domain of thyroglobulin is a protein module (Thyr-1) that occurs in a variety of secreted and membrane proteins. Several examples of Thyr-1 modules have been previously identified as inhibitors of the papain family of cysteine proteinases. Saxiphilin is a neurotoxin-binding protein from bullfrog and a homolog of transferrin with a pair of such Thyr-1 modules located in the N-lobe. Saxiphilin is now characterized as a potent inhibitor of three cysteine proteinases as follows: papain, human cathepsin B, and cathepsin L. The stoichiometry of enzyme inhibition reveals that both Thyr-1 domains of saxiphilin inhibit papain (apparent K_i = 1.72 nM), but only one of these domains inhibits cathepsin B (K_i = 1.67 nM) and cathepsin L (K_i = 0.02 nM). Physical association of saxiphilin and papain blocked from turnover at the active-site cysteine residue can be detected by cross-linking with glutaraldehyde. The rate of association of saxiphilin and cathepsin B is strongly pH-dependent with an optimum at pH 5.2, reflecting control by at least two H⁺-titratable groups. These results further demonstrate that various Thyr-1 domains are selective inhibitors of cysteine proteinases with utility in the study of protein interactions and degradation.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. Novinec, D. Kordis, V. Turk, and B. Lenarcic Diversity and Evolution of the Thyroglobulin Type-1 Domain Superfamily Mol. Biol. Evol., April 1, 2006; 23(4): 744 - 755. [Abstract] [Full Text] [PDF]

				M. Trexler, L. Bányai, and L. Patthy A human protein containing multiple types of protease-inhibitory modules PNAS, March 7, 2001; (2001) 61028398. [Abstract] [Full Text]

				M. Trexler, L. Banyai, and L. Patthy A human protein containing multiple types of protease-inhibitory modules PNAS, March 27, 2001; 98(7): 3705 - 3709. [Abstract] [Full Text] [PDF]