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J. Biol. Chem., Vol. 276, Issue 15, 12055-12059, April 13, 2001
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From the The crystal structure of the tissue-type
transglutaminase from red sea bream liver (fish-derived
transglutaminase, FTG) has been determined at 2.5-Å resolution using
the molecular replacement method, based on the crystal structure of
human blood coagulation factor XIII, which is a transglutaminase
zymogen. The model contains 666 residues of a total of 695 residues,
382 water molecules, and 1 sulfate ion. FTG consists of four domains,
and its overall and active site structures are similar to those of
human factor XIII. However, significant structural differences are
observed in both the acyl donor and acyl acceptor binding sites, which account for the difference in substrate preferences. The active site of
the enzyme is inaccessible to the solvent, because the catalytic
Cys-272 hydrogen-bonds to Tyr-515, which is thought to be displaced
upon acyl donor binding to FTG. It is postulated that the binding of an
inappropriate substrate to FTG would lead to inactivation of the enzyme
because of the formation of a new disulfide bridge between Cys-272 and
the adjacent Cys-333 immediately after the displacement of Tyr-515.
Considering the mutational studies previously reported on the
tissue-type transglutaminases, we propose that Cys-333 and Tyr-515 are
important in strictly controlling the enzymatic activity of
FTG.
The atomic coordinates and the structure factors (code 1G0D) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
Crystal Structure of Red Sea Bream Transglutaminase*
,
,
,
¶
Central Research Laboratories and
§ Food Research & Development Laboratories, Ajinomoto
Company Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki,
Kanagawa 210-8681, Japan
*
This study was supported in part by the Sakabe project of
the Tsukuba Advanced Research Alliance.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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