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| | <StructureSection load='1j4x' size='340' side='right'caption='[[1j4x]], [[Resolution|resolution]] 2.75Å' scene=''> | | <StructureSection load='1j4x' size='340' side='right'caption='[[1j4x]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1j4x]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1f5d 1f5d]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J4X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1J4X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1j4x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1f5d 1f5d]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1J4X FirstGlance]. <br> |
| | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=AHP:2-AMINO-HEPTANOIC+ACID'>AHP</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=AHP:2-AMINO-HEPTANOIC+ACID'>AHP</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1j4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j4x OCA], [http://pdbe.org/1j4x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1j4x RCSB], [http://www.ebi.ac.uk/pdbsum/1j4x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1j4x ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1j4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j4x OCA], [https://pdbe.org/1j4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1j4x RCSB], [https://www.ebi.ac.uk/pdbsum/1j4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1j4x ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DUS3_HUMAN DUS3_HUMAN]] Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines. Specifically dephosphorylates and inactivates ERK1 and ERK2.<ref>PMID:10224087</ref> <ref>PMID:11863439</ref> | + | [[https://www.uniprot.org/uniprot/DUS3_HUMAN DUS3_HUMAN]] Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines. Specifically dephosphorylates and inactivates ERK1 and ERK2.<ref>PMID:10224087</ref> <ref>PMID:11863439</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[MAP kinase phosphatase|MAP kinase phosphatase]] | + | *[[Dual specificity phosphatase 3D structures|Dual specificity phosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Structural highlights
Function
[DUS3_HUMAN] Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines. Specifically dephosphorylates and inactivates ERK1 and ERK2.[1] [2]
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
Human VHR (vaccinia H1 related phosphatase) is a member of the dual-specificity phosphatases (DSPs) that often act on bisphosphorylated protein substrates. Unlike most DSPs, VHR displays a strong preference for dephosphorylating phosphotyrosine residues over phosphothreonine residues. Here we describe the 2.75 A crystal structure of the C124S inactive VHR mutant in complex with a bisphosphorylated peptide corresponding to the MAP kinase activation lip. This structure and subsequent biochemical studies revealed the basis for the strong preference for hydrolyzing phosphotyrosine within bisphosphorylated substrates containing -pTXpY-. In the structure, the two phospho residues are oriented into distinct pockets; the phosphotyrosine is bound in the exposed yet deep active site cleft while the phosphothreonine is loosely tethered into a nearby basic pocket containing Arg(158). As this structure is the first substrate-enzyme complex reported for the DSP family of enzymes, these results provide the first glimpse into how DSPs bind their protein substrates.
Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein Phosphatase.,Schumacher MA, Todd JL, Rice AE, Tanner KG, Denu JM Biochemistry. 2002 Mar 5;41(9):3009-17. PMID:11863439[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Todd JL, Tanner KG, Denu JM. Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase VHR. A novel role in down-regulating the ERK pathway. J Biol Chem. 1999 May 7;274(19):13271-80. PMID:10224087
- ↑ Schumacher MA, Todd JL, Rice AE, Tanner KG, Denu JM. Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein Phosphatase. Biochemistry. 2002 Mar 5;41(9):3009-17. PMID:11863439
- ↑ Schumacher MA, Todd JL, Rice AE, Tanner KG, Denu JM. Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein Phosphatase. Biochemistry. 2002 Mar 5;41(9):3009-17. PMID:11863439
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