7r4l: Difference between revisions

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<StructureSection load='7r4l' size='340' side='right'caption='[[7r4l]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='7r4l' size='340' side='right'caption='[[7r4l]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7r4l]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R4L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4L FirstGlance]. <br>
<table><tr><td colspan='2'>[[7r4l]] 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=7R4L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4L FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/NAD(+)_kinase NAD(+) kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.23 2.7.1.23] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=7r4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4l OCA], [https://pdbe.org/7r4l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4l RCSB], [https://www.ebi.ac.uk/pdbsum/7r4l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4l 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=7r4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4l OCA], [https://pdbe.org/7r4l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4l RCSB], [https://www.ebi.ac.uk/pdbsum/7r4l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4l ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[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.  
[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 ==
[[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>
[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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


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>
==See Also==
 
*[[NAD kinase|NAD kinase]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7r4l" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Gelin, M]]
[[Category: Gelin M]]
[[Category: Labesse, G]]
[[Category: Labesse G]]
[[Category: Lionne, C]]
[[Category: Lionne C]]
[[Category: Mary, C]]
[[Category: Mary C]]
[[Category: Nadp bound form with iron]]
[[Category: Transferase]]

Latest revision as of 10:54, 1 May 2024

Crystal structure of human mitochondrial NAD kinaseCrystal structure of human mitochondrial NAD kinase

Structural highlights

7r4l is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

NAKD2_HUMAN Progressive encephalopathy with leukodystrophy due to DECR deficiency. The disease is caused by variants affecting the gene represented in this entry.

Function

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.[1]

See Also

References

  1. ↑ Ohashi K, Kawai S, Murata K. Identification and characterization of a human mitochondrial NAD kinase. Nat Commun. 2012;3:1248. doi: 10.1038/ncomms2262. PMID:23212377 doi:http://dx.doi.org/10.1038/ncomms2262

7r4l, resolution 2.60Å

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