2Q3Z

Transglutaminase 2 undergoes large conformational change upon activation

2Q3Z の概要

• エントリーDOI: 10.2210/pdb2q3z/pdb
• 関連するPDBエントリー: 1kv3
• 分子名称: Transglutaminase 2, Polypeptide, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: transglutaminase 2, tissue transglutaminase, tg2, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 78445.68

構造登録者

Strop, P.,Pinkas, D.M.,Brunger, A.T.,Khosla, C. (登録日: 2007-05-30, 公開日: 2007-10-23, 最終更新日: 2023-11-15)

主引用文献

Pinkas, D.M.,Strop, P.,Brunger, A.T.,Khosla, C.
Transglutaminase 2 undergoes a large conformational change upon activation
Plos Biol., 5:e327-e327, 2007

PubMed Abstract: 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.

PubMed: 18092889
DOI: 10.1371/journal.pbio.0050327

実験手法

X-RAY DIFFRACTION (2 Å)