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4dzy

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4dzy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DZY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DZY FirstGlance]. <br>
<table><tr><td colspan='2'>[[4dzy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DZY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DZY FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=WJ1:(S)-2-CHLORO-3-PHENYLPROPANOIC+ACID'>WJ1</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.101&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=WJ1:(S)-2-CHLORO-3-PHENYLPROPANOIC+ACID'>WJ1</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=4dzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dzy OCA], [https://pdbe.org/4dzy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dzy RCSB], [https://www.ebi.ac.uk/pdbsum/4dzy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dzy 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=4dzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dzy OCA], [https://pdbe.org/4dzy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dzy RCSB], [https://www.ebi.ac.uk/pdbsum/4dzy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dzy ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/BCKD_RAT BCKD_RAT]] Catalyzes the phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex, the key regulatory enzyme of the valine, leucine and isoleucine catabolic pathways. Key enzyme that regulate the activity state of the BCKD complex.
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[https://www.uniprot.org/uniprot/BCKD_RAT BCKD_RAT] Catalyzes the phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex, the key regulatory enzyme of the valine, leucine and isoleucine catabolic pathways. Key enzyme that regulate the activity state of the BCKD complex.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are elevated in maple syrup urine disease, heart failure, obesity, and type 2 diabetes. BCAA homeostasis is controlled by the mitochondrial branched-chain alpha-ketoacid dehydrogenase complex (BCKDC), which is negatively regulated by the specific BCKD kinase (BDK). Here, we used structure-based design to develop a BDK inhibitor, (S)-alpha-chloro-phenylpropionic acid [(S)-CPP]. Crystal structures of the BDK-(S)-CPP complex show that (S)-CPP binds to a unique allosteric site in the N-terminal domain, triggering helix movements in BDK. These conformational changes are communicated to the lipoyl-binding pocket, which nullifies BDK activity by blocking its binding to the BCKDC core. Administration of (S)-CPP to mice leads to the full activation and dephosphorylation of BCKDC with significant reduction in plasma BCAA concentrations. The results buttress the concept of targeting mitochondrial BDK as a pharmacological approach to mitigate BCAA accumulation in metabolic diseases and heart failure.
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Structure-based design and mechanisms of allosteric inhibitors for mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase.,Tso SC, Qi X, Gui WJ, Chuang JL, Morlock LK, Wallace AL, Ahmed K, Laxman S, Campeau PM, Lee BH, Hutson SM, Tu BP, Williams NS, Tambar UK, Wynn RM, Chuang DT Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9728-33. doi:, 10.1073/pnas.1303220110. Epub 2013 May 28. PMID:23716694<ref>PMID:23716694</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4dzy" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>

Current revision

Crystal structure of branched-chain alpha-ketoacid dehydrogenase kinase/(S)-2-chloro-3-phenylpropanoic acid complex with ADP

PDB ID 4dzy

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