4da1: Difference between revisions
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==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=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4da1]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DA1 FirstGlance]. <br> | |||
==Disease== | </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> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2iq1|2iq1]]</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 Homo sapiens])</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://www.rcsb.org/pdb/explore.do?structureId=4da1 RCSB], [http://www.ebi.ac.uk/pdbsum/4da1 PDBsum]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/PPM1K_HUMAN PPM1K_HUMAN]] Intermediate maple syrup urine disease. | [[http://www.uniprot.org/uniprot/PPM1K_HUMAN PPM1K_HUMAN]] Intermediate maple syrup urine disease. | ||
== 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> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:22291014</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Protein phosphatase|Protein phosphatase]] | *[[Protein phosphatase|Protein phosphatase]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Phosphoprotein phosphatase]] | [[Category: Phosphoprotein phosphatase]] | ||
[[Category: Brautigam, C A | [[Category: Brautigam, C A]] | ||
[[Category: Chuang, D T | [[Category: Chuang, D T]] | ||
[[Category: Chuang, J L | [[Category: Chuang, J L]] | ||
[[Category: Dehydrogenase phosphatase]] | [[Category: Dehydrogenase phosphatase]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Metal-ion-assisted catalysis]] | [[Category: Metal-ion-assisted catalysis]] | ||
[[Category: Mitochondria]] | [[Category: Mitochondria]] | ||
