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Title
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Three-dimensional structure of the human transglutaminase 3 enzyme: binding of calcium ions changes structure for activation.
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Authors
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B.Ahvazi,
H.C.Kim,
S.H.Kee,
Z.Nemes,
P.M.Steinert.
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Ref.
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EMBO J, 2002,
21,
2055-2067.
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PubMed id
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Abstract
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Transglutaminase (TGase) enzymes catalyze the formation of covalent cross-links
between protein-bound glutamines and lysines in a calcium-dependent manner, but
the role of Ca(2+) ions remains unclear. The TGase 3 isoform is widely expressed
and is important for epithelial barrier formation. It is a zymogen, requiring
proteolysis for activity. We have solved the three-dimensional structures of the
zymogen and the activated forms at 2.2 and 2.1 A resolution, respectively, and
examined the role of Ca(2+) ions. The zymogen binds one ion tightly that cannot
be exchanged. Upon proteolysis, the enzyme exothermally acquires two more Ca(2+)
ions that activate the enzyme, are exchangeable and are functionally replaceable
by other lanthanide trivalent cations. Binding of a Ca(2+) ion at one of these
sites opens a channel which exposes the key Trp236 and Trp327 residues that
control substrate access to the active site. Together, these biochemical and
structural data reveal for the first time in a TGase enzyme that Ca(2+) ions
induce structural changes which at least in part dictate activity and, moreover,
may confer substrate specificity.
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