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1j4x

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HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE C124S MUTANT-PEPTIDE COMPLEX

Structural highlights

1j4x is a 2 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1f5d. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.75Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1j4x"

@@ Line 3: / Line 3: @@
 <StructureSection load='1j4x' size='340' side='right'caption='[[1j4x]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<table><tr><td colspan='2'>[[1j4x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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>
 == Function ==
-[[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>
+[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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 36: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Protein-tyrosine-phosphatase]]
+[[Category: Denu JM]]
-[[Category: Denu, J M]]
+[[Category: Schumacher MA]]
-[[Category: Schumacher, M A]]
+[[Category: Tanner KG]]
-[[Category: Tanner, K G]]
+[[Category: Todd JL]]
-[[Category: Todd, J L]]
-[[Category: Hydrolase]]
-[[Category: Protein dual-specificity phosphatase]]

1j4x

From Proteopedia

Current revision

HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE C124S MUTANT-PEPTIDE COMPLEX

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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