2img | pdb_00002img

Crystal structure of dual specificity protein phosphatase 23 from Homo sapiens in complex with ligand malate ion

spinqualitylabelsall models 2img, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2img is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MLT NonStd Res: MSE Gene: DUSP23 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, TOPSAN Function [DUS23_HUMAN] Protein phosphatase that mediates dephosphorylation of proteins phosphorylated on Tyr and Ser/Thr residues. In vitro, it can dephosphorylate p44-ERK1 (MAPK3) but not p54 SAPK-beta (MAPK10) in vitro. Able to enhance activation of JNK and p38 (MAPK14). 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 Protein phosphorylation plays a crucial role in mitogenic signal transduction and regulation of cell growth and differentiation. Dual specificity protein phosphatase 23 (DUSP23) or VHZ mediates dephosphorylation of phospho-tyrosyl (pTyr) and phospho-seryl/threonyl (pSer/pThr) residues in specific proteins. In vitro, it can dephosphorylate p44ERK1 but not p54SAPK-beta and enhance activation of c-Jun N-terminal kinase (JNK) and p38. Human VHZ, the smallest of the catalytically active protein-tyrosine phosphatases (PTP) reported to date (150 residues), is a class I Cys-based PTP and bears the distinctive active site signature motif HCXXGXXRS(T). We present the crystal structure of VHZ determined at 1.93A resolution. The polypeptide chain adopts the typical alphabetaalpha PTP fold, giving rise to a shallow active site cleft that supports dual phosphorylated substrate specificity. Within our crystals, the Thr-135-Tyr-136 from a symmetry-related molecule bind in the active site with a malate ion, where they mimic the phosphorylated TY motif of the MAPK activation loop in an enzyme-substrate/product complex. Analyses of intermolecular interactions between the enzyme and this pseudo substrate/product along with functional analysis of Phe-66, Leu-97, and Phe-99 residues provide insights into the mechanism of substrate binding and catalysis in VHZ. Structure of human dual specificity protein phosphatase 23, VHZ, enzyme-substrate/product complex.,Agarwal R, Burley SK, Swaminathan S J Biol Chem. 2008 Apr 4;283(14):8946-53. Epub 2008 Feb 1. PMID:18245086 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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