A model for the reaction mechanism of the transglutaminase 3 enzyme.

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Ahvazi B, Steinert PM

A model for the reaction mechanism of the transglutaminase 3 enzyme.

Exp Mol Med. 2003 Aug 31;35(4):228-42.

PubMed ID

14508061 [ View in PubMed

]

Abstract

Transglutaminase enzymes (TGases) catalyze the calcium dependent formation of an isopeptide bond between protein-bound glutamine and lysine substrates. Previously we have shown that activated TGase 3 acquires two additional calcium ions at site two and three. The calcium ion at site three results in the opening of a channel. At this site, the channel opening and closing could modulate, depending on which metal is bound. Here we propose that the front of the channel could be used by the two substrates for enzyme reaction. We propose that the glutamine substrate is directed from Trp236 into the enzyme, shown by molecular docking. Then a lysine substrate approaches the opened active site to engage Trp327, leading to formation of the isopeptide bond. Further, direct comparisons of the structures of TGase 3 with other TGases have allowed us to identify several residues that might potentially be involved in generic and specific recognition of the glutamine and lysine substrates.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
L-Glutamine	Protein-glutamine gamma-glutamyltransferase E	Protein	Humans	Unknown	Substrate	Details