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| | ==Crystal structure of branched-chain alpha-ketoacid dehydrogenase phosphatase with Mg (II) ions at the active site== | | ==Crystal structure of branched-chain alpha-ketoacid dehydrogenase phosphatase with Mg (II) ions at the active site== |
| - | <StructureSection load='4da1' size='340' side='right' caption='[[4da1]], [[Resolution|resolution]] 2.38Å' scene=''> | + | <StructureSection load='4da1' size='340' side='right'caption='[[4da1]], [[Resolution|resolution]] 2.38Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4da1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DA1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DA1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4da1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DA1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DA1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2iq1|2iq1]]</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=4da1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da1 OCA], [https://pdbe.org/4da1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4da1 RCSB], [https://www.ebi.ac.uk/pdbsum/4da1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4da1 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPM1K, PP2CM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </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=4da1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da1 OCA], [http://pdbe.org/4da1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4da1 RCSB], [http://www.ebi.ac.uk/pdbsum/4da1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4da1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PPM1K_HUMAN PPM1K_HUMAN]] Intermediate maple syrup urine disease. | + | [[https://www.uniprot.org/uniprot/PPM1K_HUMAN PPM1K_HUMAN]] Intermediate maple syrup urine disease. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PPM1K_HUMAN PPM1K_HUMAN]] Regulates the mitochondrial permeability transition pore and is essential for cellular survival and development.<ref>PMID:17374715</ref> | + | [[https://www.uniprot.org/uniprot/PPM1K_HUMAN PPM1K_HUMAN]] Regulates the mitochondrial permeability transition pore and is essential for cellular survival and development.<ref>PMID:17374715</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4da1" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4da1" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Phosphoprotein phosphatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Brautigam, C A]] | + | [[Category: Brautigam CA]] |
| - | [[Category: Chuang, D T]] | + | [[Category: Chuang DT]] |
| - | [[Category: Chuang, J L]] | + | [[Category: Chuang JL]] |
| - | [[Category: Dehydrogenase phosphatase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metal-ion-assisted catalysis]]
| + | |
| - | [[Category: Mitochondria]]
| + | |
| Structural highlights
Disease
[PPM1K_HUMAN] Intermediate maple syrup urine disease.
Function
[PPM1K_HUMAN] Regulates the mitochondrial permeability transition pore and is essential for cellular survival and development.[1]
Publication Abstract from PubMed
The branched-chain alpha-ketoacid dehydrogenase phosphatase (BDP) component of the human branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) has been expressed in Escherichia coli and purified in the soluble form. The monomeric BDP shows a strict dependence on Mn(2+) ions for phosphatase activity, whereas Mg(2+) and Ca(2+) ions do not support catalysis. Metal binding constants for BDP, determined by competition isothermal titration calorimetry, are 2.4 nm and 10 mum for Mn(2+) and Mg(2+) ions, respectively. Using the phosphorylated decarboxylase component (p-E1b) of BCKDC as a substrate, BDP shows a specific activity of 68 nmol/min/mg. The Ca(2+)-independent binding of BDP to the 24-meric transacylase (dihydrolipoyl transacylase; E2b) core of BCKDC results in a 3-fold increase in the dephosphorylation rate of p-E1b. However, the lipoyl prosthetic group on E2b is not essential for BDP binding or E2b-stimulated phosphatase activity. Acidic residues in the C-terminal linker of the E2b lipoyl domain are essential for the interaction between BDP and E2b. The BDP structure was determined by x-ray crystallography to 2.4 A resolution. The BDP structure is dominated by a central beta-sandwich. There are two protrusions forming a narrow cleft approximately 10 A wide, which constitutes the active site. The carboxylate moieties of acidic residues Asp-109, Asp-207, Asp-298, and Asp-337 in the active-site cleft participate in binding two metal ions. Substitutions of these residues with alanine nullify BDP phosphatase activity. Alteration of the nearby Arg-104 increases the K(m) for p-E1b peptide by 60-fold, suggesting that this residue is critical for the recognition of the native p-E1b protein.
Structural and biochemical characterization of human mitochondrial branched-chain alpha-ketoacid dehydrogenase phosphatase.,Wynn RM, Li J, Brautigam CA, Chuang JL, Chuang DT J Biol Chem. 2012 Mar 16;287(12):9178-92. Epub 2012 Jan 30. PMID:22291014[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lu G, Ren S, Korge P, Choi J, Dong Y, Weiss J, Koehler C, Chen JN, Wang Y. A novel mitochondrial matrix serine/threonine protein phosphatase regulates the mitochondria permeability transition pore and is essential for cellular survival and development. Genes Dev. 2007 Apr 1;21(7):784-96. Epub 2007 Mar 20. PMID:17374715 doi:http://dx.doi.org/10.1101/gad.1499107
- ↑ Wynn RM, Li J, Brautigam CA, Chuang JL, Chuang DT. Structural and biochemical characterization of human mitochondrial branched-chain alpha-ketoacid dehydrogenase phosphatase. J Biol Chem. 2012 Mar 16;287(12):9178-92. Epub 2012 Jan 30. PMID:22291014 doi:10.1074/jbc.M111.314963
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