2IMG

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

2IMG の概要

• エントリーDOI: 10.2210/pdb2img/pdb
• 分子名称: Dual specificity protein phosphatase 23, D-MALATE (3 entities in total)
• 機能のキーワード: dusp23, vhz, ldp-3, dual specicity protein phosphatase 23, dus23_human, malate, 8673a, structural genomics, psi, protein structure initiative, new york sgx research center for structural genomics, nysgxrc, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16860.16

構造登録者

Agarwal, R.,Burley, S.K.,Swaminathan, S.,New York SGX Research Center for Structural Genomics (NYSGXRC) (登録日: 2006-10-04, 公開日: 2006-10-17, 最終更新日: 2024-10-30)

主引用文献

Agarwal, R.,Burley, S.K.,Swaminathan, S.
Structure of human dual specificity protein phosphatase 23, VHZ, enzyme-substrate/product complex.
J.Biol.Chem., 283:8946-8953, 2008

PubMed Abstract: 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.

PubMed: 18245086
DOI: 10.1074/jbc.M708945200

実験手法

X-RAY DIFFRACTION (1.93 Å)