2A8I

Crystal Structure of human Taspase1

2A8I の概要

• エントリーDOI: 10.2210/pdb2a8i/pdb
• 分子名称: Threonine aspartase 1 (2 entities in total)
• 機能のキーワード: taspase1, asparaginase, glycosylspaginse, mll, threonine aspartase, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 89683.47

構造登録者

Khan, J.A.,Dunn, B.M.,Tong, L. (登録日: 2005-07-08, 公開日: 2005-11-01, 最終更新日: 2024-10-16)

主引用文献

Khan, J.A.,Dunn, B.M.,Tong, L.
Crystal Structure of Human Taspase1, a Crucial Protease Regulating the Function of MLL.
Structure, 13:1443-1452, 2005

PubMed Abstract: Taspase1 catalyzes the proteolytic processing of the mixed lineage leukemia (MLL) nuclear protein, which is required for maintaining Hox gene expression patterns. Chromosomal translocations of the MLL gene are associated with leukemia in infants. Taspase1, a threonine aspartase, is a member of the type 2 asparaginase family, but is the only protease in this family. We report here the crystal structures of human activated Taspase1 and its proenzyme, as well as the characterization of the effects of mutations in the active site region using a newly developed fluorogenic assay. The structure of Taspase1 has significant differences from other asparaginases, especially near the active site. Mutation of the catalytic nucleophile, Thr234, abolishes autocatalytic processing in cis but does not completely block proteolysis in trans. The structure unexpectedly showed the binding of a chloride ion in the active site, and our kinetic studies confirm that chlorides ions are inhibitors of this enzyme at physiologically relevant concentrations.

PubMed: 16216576
DOI: 10.1016/j.str.2005.07.006

実験手法

X-RAY DIFFRACTION (2 Å)