1nuf
Role of Calcium Ions in the Activation and Activity of the Transglutaminase 3 Enzyme
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OverviewOverview
The transglutaminase 3 enzyme is widely expressed in many tissues, including epithelia. We have shown previously that it can bind three Ca2+, ions, which in site one is constitutively bound, while those in sites two, and three are acquired during activation and are required for activity. In, particular, binding at site three opens a channel through the enzyme and, exposes two tryptophan residues near the active site that are thought to, be important for enzyme reaction. In this study, we have solved the, structures of three more forms of this enzyme by x-ray crystallography in, the presence of Ca2+ and/or Mg2+, which provide new insights on the, precise contribution of each Ca2+ ion to activation and activity. First, we found that Ca2+ ion in site one can be exchanged with difficulty, and, it has a binding affinity of Kd = 0.3 microm (DeltaH = -6.70 +/- 0.52, kcal/mol), which suggests it is important for the stabilization of the, enzyme. Site two can be occupied by some lanthanides but only Ca2+ of the, Group 2 family of alkali earth metals, and its occupancy are required for, activity. Site three can be occupied by some lanthanides, Ca2+,or Mg2+;, however, when Mg2+ is present, the enzyme is inactive, and the channel is, closed. Thus Ca2+ binding in both sites two and three cooperate in opening, the channel. We speculate that manipulation of the channel opening could, be controlled by intracellular cation levels. Together, these data have, important implications for reaction mechanism of the enzyme: the opening, of a channel perhaps controls access to and manipulation of substrates at, the active site.
About this StructureAbout this Structure
1NUF is a Single protein structure of sequence from Homo sapiens with CL, BR and CA as ligands. Active as Protein-glutamine gamma-glutamyltransferase, with EC number 2.3.2.13 Full crystallographic information is available from OCA.
ReferenceReference
Roles of calcium ions in the activation and activity of the transglutaminase 3 enzyme., Ahvazi B, Boeshans KM, Idler W, Baxa U, Steinert PM, J Biol Chem. 2003 Jun 27;278(26):23834-41. Epub 2003 Apr 4. PMID:12679341
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