2q3z
From Proteopedia
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Transglutaminase 2 undergoes large conformational change upon activation
Overview
Human transglutaminase 2 (TG2), a member of a large family of enzymes that, catalyze protein crosslinking, plays an important role in the, extracellular matrix biology of many tissues and is implicated in the, gluten-induced pathogenesis of celiac sprue. Although vertebrate, transglutaminases have been studied extensively, thus far all structurally, characterized members of this family have been crystallized in, conformations with inaccessible active sites. We have trapped human TG2 in, complex with an inhibitor that mimics inflammatory gluten peptide, substrates and have solved, at 2-A resolution, its x-ray crystal, structure. The inhibitor stabilizes TG2 in an extended conformation that, is dramatically different from earlier transglutaminase structures. The, active site is exposed, revealing that catalysis takes place in a tunnel, bridged by two tryptophan residues that separate acyl-donor from, acyl-acceptor and stabilize the tetrahedral reaction intermediates., Site-directed mutagenesis was used to investigate the acyl-acceptor side, of the tunnel, yielding mutants with a marked increase in preference for, hydrolysis over transamidation. By providing the ability to visualize this, activated conformer, our results create a foundation for understanding the, catalytic as well as the non-catalytic roles of TG2 in biology, and for, dissecting the process by which the autoantibody response to TG2 is, induced in celiac sprue patients.
About this Structure
2Q3Z is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Protein-glutamine gamma-glutamyltransferase, with EC number 2.3.2.13 Full crystallographic information is available from OCA.
Reference
Transglutaminase 2 undergoes a large conformational change upon activation., Pinkas DM, Strop P, Brunger AT, Khosla C, PLoS Biol. 2007 Dec;5(12):e327. PMID:18092889
Page seeded by OCA on Wed Jan 23 11:02:13 2008
