7r4j

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7r4j]] 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=7R4J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4J FirstGlance]. <br>
<table><tr><td colspan='2'>[[7r4j]] 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=7R4J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4J 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=CA:CALCIUM+ION'>CA</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]] 2.95&#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=CA:CALCIUM+ION'>CA</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=7r4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4j OCA], [https://pdbe.org/7r4j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4j RCSB], [https://www.ebi.ac.uk/pdbsum/7r4j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4j 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=7r4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4j OCA], [https://pdbe.org/7r4j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4j RCSB], [https://www.ebi.ac.uk/pdbsum/7r4j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4j ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[https://www.uniprot.org/uniprot/NAKD2_HUMAN NAKD2_HUMAN]] Progressive encephalopathy with leukodystrophy due to DECR deficiency. The disease is caused by variants affecting the gene represented in this entry.
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[https://www.uniprot.org/uniprot/NAKD2_HUMAN NAKD2_HUMAN] Progressive encephalopathy with leukodystrophy due to DECR deficiency. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/NAKD2_HUMAN NAKD2_HUMAN]] Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor. Also has weak NADH kinase activity in vitro; however NADH kinase activity is much weaker than the NAD(+) kinase activity and may not be relevant in vivo.<ref>PMID:23212377</ref>
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[https://www.uniprot.org/uniprot/NAKD2_HUMAN NAKD2_HUMAN] Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor. Also has weak NADH kinase activity in vitro; however NADH kinase activity is much weaker than the NAD(+) kinase activity and may not be relevant in vivo.<ref>PMID:23212377</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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NAD(+) kinases (NADKs) are metabolite kinases that phosphorylate NAD(+) molecules to make NADP(+), a limiting substrate for the generation of reducing power NADPH. NADK2 sustains mitochondrial NADPH production that enables proline biosynthesis and antioxidant defense. However, its molecular architecture and mechanistic regulation remain undescribed. Here, we report the crystal structure of human NADK2, revealing a substrate-driven mode of activation. We find that NADK2 presents an unexpected dimeric organization instead of the typical tetrameric assemblage observed for other NADKs. A specific extended segment (aa 325-365) is crucial for NADK2 dimerization and activity. Moreover, we characterize numerous acetylation events, including those on Lys76 and Lys304, which reside near the active site and inhibit NADK2 activity without disrupting dimerization, thereby reducing mitochondrial NADP(H) production, proline synthesis, and cell growth. These findings reveal important molecular insight into the structure and regulation of a vital enzyme in mitochondrial NADPH and proline metabolism.
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Crystal structure of human NADK2 reveals a dimeric organization and active site occlusion by lysine acetylation.,Mary C, Soflaee MH, Kesavan R, Gelin M, Brown H, Zacharias G, Mathews TP, Lemoff A, Lionne C, Labesse G, Hoxhaj G Mol Cell. 2022 Jul 13. pii: S1097-2765(22)00609-8. doi:, 10.1016/j.molcel.2022.06.026. PMID:35868311<ref>PMID:35868311</ref>
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==See Also==
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*[[NAD kinase|NAD kinase]]
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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 7r4j" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>

Current revision

Crystal structure of human mitochondrial NAD kinase

PDB ID 7r4j

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