2IMG

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

Summary for 2IMG

• Entry DOI: 10.2210/pdb2img/pdb
• Descriptor: Dual specificity protein phosphatase 23, D-MALATE (3 entities in total)
• Functional Keywords: 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
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 16860.16

Authors

Agarwal, R.,Burley, S.K.,Swaminathan, S.,New York SGX Research Center for Structural Genomics (NYSGXRC) (deposition date: 2006-10-04, release date: 2006-10-17, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.93 Å)