7r4k - Revision history

OCA at 07:54, 1 May 2024

2024-05-01T07:54:29Z

←Older revision		Revision as of 07:54, 1 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7r4k]] 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=7R4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4K FirstGlance]. <br>		<table><tr><td colspan='2'>[[7r4k]] 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=7R4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4K FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 3.33Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7r4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4k OCA], [https://pdbe.org/7r4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4k RCSB], [https://www.ebi.ac.uk/pdbsum/7r4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4k 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=7r4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4k OCA], [https://pdbe.org/7r4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4k RCSB], [https://www.ebi.ac.uk/pdbsum/7r4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4k 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®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 7r4k" style~~=~~"background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>

OCA at 03:51, 8 September 2022

2022-09-08T03:51:21Z

←Older revision		Revision as of 03:51, 8 September 2022
Line 3:		Line 3:
	<StructureSection load='7r4k' size='340' side='right'caption='[[7r4k]], [[Resolution\|resolution]] 3.33Å' scene=''>		<StructureSection load='7r4k' size='340' side='right'caption='[[7r4k]], [[Resolution\|resolution]] 3.33Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7r4k]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4K FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7r4k]] 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=7R4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4K FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7r4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4k OCA], [https://pdbe.org/7r4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4k RCSB], [https://www.ebi.ac.uk/pdbsum/7r4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4k 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=7r4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4k OCA], [https://pdbe.org/7r4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4k RCSB], [https://www.ebi.ac.uk/pdbsum/7r4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4k 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 24:
	__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 magnesium]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 05:00, 3 August 2022

2022-08-03T05:00:36Z

←Older revision		Revision as of 05:00, 3 August 2022
Line 1:		Line 1:

	==Crystal structure of human mitochondrial NAD kinase==		==Crystal structure of human mitochondrial NAD kinase==
-	<StructureSection load='7r4k' size='340' side='right'caption='[[7r4k]]' scene=''>	+	<StructureSection load='7r4k' size='340' side='right'caption='[[7r4k]], [[Resolution\|resolution]] 3.33Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4K FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7r4k]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4K FirstGlance]. <br>
-	</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=7r4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4k OCA], [https://pdbe.org/7r4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4k RCSB], [https://www.ebi.ac.uk/pdbsum/7r4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4k ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7r4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4k OCA], [https://pdbe.org/7r4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4k RCSB], [https://www.ebi.ac.uk/pdbsum/7r4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4k ProSAT]</span></td></tr>
	</table>		</table>
		+	== 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.
		+	== 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>
		+	<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>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7r4k" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[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 magnesium]]
		+	[[Category: Transferase]]

OCA at 16:13, 6 July 2022

2022-07-06T16:13:09Z

←Older revision		Revision as of 16:13, 6 July 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7r4k is ~~ON HOLD~~	+	==Crystal structure of human mitochondrial NAD kinase==
-		+	<StructureSection load='7r4k' size='340' side='right'caption='[[7r4k]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4K FirstGlance]. <br>
-	~~Description~~:	+	</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=7r4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4k OCA], [https://pdbe.org/7r4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4k RCSB], [https://www.ebi.ac.uk/pdbsum/7r4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4k ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Gelin M]]
		+	[[Category: Labesse G]]
		+	[[Category: Lionne C]]
		+	[[Category: Mary C]]

OCA at 06:03, 29 June 2022

2022-06-29T06:03:05Z

←Older revision		Revision as of 06:03, 29 June 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7r4k is ON HOLD ~~until Paper Publication~~	+	The entry 7r4k is ON HOLD

	Authors:		Authors:

OCA at 06:26, 23 February 2022

2022-02-23T06:26:58Z

←Older revision		Revision as of 06:26, 23 February 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7r4k is ON HOLD	+	The entry 7r4k is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7r4k" [edit=sysop:move=sysop]

2022-02-16T09:03:22Z

Protected "7r4k" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:03, 16 February 2022

OCA: New page: '''Unreleased structure''' The entry 7r4k is ON HOLD Authors: Description: Category: Unreleased Structures

2022-02-16T09:03:21Z

New page: '''Unreleased structure''' The entry 7r4k is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7r4k is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]