7zpe: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 7zpe is ~~ON HOLD~~

==human branched Chain Keto Acid Dehydrogenase Kinase in complex with ligand==

~~Authors~~: ~~Kack~~, H., ~~Wissler~~, L.

== Structural highlights ==

<table><tr><td colspan='2'>[[7zpe]] 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=7ZPE OCA]. For a guided tour on the structure components use [https://proteopedia.org/fgij/fg.htm?mol=7ZPE FirstGlance].

~~Description~~: ~~human~~ branched ~~Chain Keto Acid Dehydrogenase Kinase~~ in complex with ~~ligand~~

</td></tr><tr id='method'><td class="sblockLbl">[[Empirical_models|Method:]]</td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.64Å</td></tr>

[[Category: ~~Unreleased Structures~~]]

<tr id='ligand'><td class="sblockLbl">[[Ligand|Ligands:]]</td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JP6:2-[(4-chlorophenyl)methylamino]-5-propyl-6~{H}-[1,2,4]triazolo[1,5-a]pyrimidin-7-one'>JP6</scene></td></tr>

[[Category: ~~Wissler, L~~]]

<tr id='resources'><td class="sblockLbl">Resources:</td><td class="sblockDat">[https://proteopedia.org/fgij/fg.htm?mol=7zpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zpe OCA], [https://pdbe.org/7zpe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zpe RCSB], [https://www.ebi.ac.uk/pdbsum/7zpe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zpe ProSAT]</td></tr>

[[Category: Kack, H]]

</table>

== Disease ==

[https://www.uniprot.org/uniprot/BCKD_HUMAN BCKD_HUMAN] Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency. The disease is caused by variants affecting the gene represented in this entry. A diet enriched in branched amino acids (BCAAs) allows to normalize plasma BCAA levels. This suggests that it may be possible to treat patients with mutations in BCKDK with BCAA supplementation.

== Function ==

[https://www.uniprot.org/uniprot/BCKD_HUMAN BCKD_HUMAN] Serine/threonine-protein kinase component of macronutrients metabolism. Forms a functional kinase and phosphatase pair with PPM1K, serving as a metabolic regulatory node that coordinates branched-chain amino acids (BCAAs) with glucose and lipid metabolism via two distinct phosphoprotein targets: mitochondrial BCKDHA subunit of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex and cytosolic ACLY, a lipogenic enzyme of Krebs cycle (PubMed:24449431, PubMed:29779826, PubMed:37558654). Phosphorylates and inactivates mitochondrial BCKDH complex a multisubunit complex consisting of three multimeric components each involved in different steps of BCAA catabolism: E1 composed of BCKDHA and BCKDHB, E2 core composed of DBT monomers, and E3 composed of DLD monomers. Associates with the E2 component of BCKDH complex and phosphorylates BCKDHA on Ser-337, leading to conformational changes that interrupt substrate channeling between E1 and E2 and inactivates the BCKDH complex (PubMed:29779826, PubMed:37558654). Phosphorylates ACLY on Ser-455 in response to changes in cellular carbohydrate abundance such as occurs during fasting to feeding metabolic transition. Refeeding stimulates MLXIPL/ChREBP transcription factor, leading to increased BCKDK to PPM1K expression ratio, phosphorylation and activation of ACLY that ultimately results in the generation of malonyl-CoA and oxaloacetate immediate substrates of de novo lipogenesis and glucogenesis, respectively (PubMed:29779826). Recognizes phosphosites having SxxE/D canonical motif (PubMed:29779826).<ref>PMID:24449431</ref> <ref>PMID:29779826</ref> <ref>PMID:37558654</ref>

== References ==

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Kack H]]

[[Category: Wissler L]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 7zpe is ON HOLD
+==human branched Chain Keto Acid Dehydrogenase Kinase in complex with ligand==
+<StructureSection load='7zpe' size='340' side='right'caption='[[7zpe]], [[Resolution|resolution]] 2.64&Aring;' scene=''>
-Authors: Kack, H., Wissler, L.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7zpe]] 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=7ZPE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZPE FirstGlance]. <br>
-Description: human branched Chain Keto Acid Dehydrogenase Kinase in complex with ligand
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.64&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JP6:2-[(4-chlorophenyl)methylamino]-5-propyl-6~{H}-[1,2,4]triazolo[1,5-a]pyrimidin-7-one'>JP6</scene></td></tr>
-[[Category: Wissler, L]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7zpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zpe OCA], [https://pdbe.org/7zpe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zpe RCSB], [https://www.ebi.ac.uk/pdbsum/7zpe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zpe ProSAT]</span></td></tr>
-[[Category: Kack, H]]
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/BCKD_HUMAN BCKD_HUMAN] Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency. The disease is caused by variants affecting the gene represented in this entry. A diet enriched in branched amino acids (BCAAs) allows to normalize plasma BCAA levels. This suggests that it may be possible to treat patients with mutations in BCKDK with BCAA supplementation.
+== Function ==
+[https://www.uniprot.org/uniprot/BCKD_HUMAN BCKD_HUMAN] Serine/threonine-protein kinase component of macronutrients metabolism. Forms a functional kinase and phosphatase pair with PPM1K, serving as a metabolic regulatory node that coordinates branched-chain amino acids (BCAAs) with glucose and lipid metabolism via two distinct phosphoprotein targets: mitochondrial BCKDHA subunit of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex and cytosolic ACLY, a lipogenic enzyme of Krebs cycle (PubMed:24449431, PubMed:29779826, PubMed:37558654). Phosphorylates and inactivates mitochondrial BCKDH complex a multisubunit complex consisting of three multimeric components each involved in different steps of BCAA catabolism: E1 composed of BCKDHA and BCKDHB, E2 core composed of DBT monomers, and E3 composed of DLD monomers. Associates with the E2 component of BCKDH complex and phosphorylates BCKDHA on Ser-337, leading to conformational changes that interrupt substrate channeling between E1 and E2 and inactivates the BCKDH complex (PubMed:29779826, PubMed:37558654). Phosphorylates ACLY on Ser-455 in response to changes in cellular carbohydrate abundance such as occurs during fasting to feeding metabolic transition. Refeeding stimulates MLXIPL/ChREBP transcription factor, leading to increased BCKDK to PPM1K expression ratio, phosphorylation and activation of ACLY that ultimately results in the generation of malonyl-CoA and oxaloacetate immediate substrates of de novo lipogenesis and glucogenesis, respectively (PubMed:29779826). Recognizes phosphosites having SxxE/D canonical motif (PubMed:29779826).<ref>PMID:24449431</ref> <ref>PMID:29779826</ref> <ref>PMID:37558654</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Kack H]]
+[[Category: Wissler L]]