2a8m

Crystal Structure of Human Taspase1 (T234S mutant)

spinqualitylabelsall models 2a8m, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2a8m is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL Related: 2a8i, 2a8j, 2a8l Gene: C20orf13 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [TASP1_HUMAN] Protease involved in MLL processing and, consequently, in the correct expression of the early HOXA gene cluster. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Crystal structure of human Taspase1, a crucial protease regulating the function of MLL.,Khan JA, Dunn BM, Tong L Structure. 2005 Oct;13(10):1443-52. PMID:16216576 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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