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| | ==Crystal structure of NAD kinase 1 from Listeria monocytogenes in complex with 2'-phosphate bis(adenosine)-5'-diphosphate== | | ==Crystal structure of NAD kinase 1 from Listeria monocytogenes in complex with 2'-phosphate bis(adenosine)-5'-diphosphate== |
| - | <StructureSection load='4dy6' size='340' side='right' caption='[[4dy6]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='4dy6' size='340' side='right'caption='[[4dy6]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4dy6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacterium_monocytogenes_hominis"_nyfeldt_1932 "bacterium monocytogenes hominis" nyfeldt 1932]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2i2e 2i2e]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DY6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DY6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4dy6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Listeria_monocytogenes Listeria monocytogenes]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2i2e 2i2e]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DY6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DY6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A22:[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL]METHYL+[(2R,3R,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3-HYDROXY-4-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]METHYL+DIHYDROGEN+DIPHOSPHATE'>A22</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A22:[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL]METHYL+[(2R,3R,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3-HYDROXY-4-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]METHYL+DIHYDROGEN+DIPHOSPHATE'>A22</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lmo0968, ppnK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1639 "Bacterium monocytogenes hominis" Nyfeldt 1932])</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=4dy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dy6 OCA], [https://pdbe.org/4dy6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dy6 RCSB], [https://www.ebi.ac.uk/pdbsum/4dy6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dy6 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_kinase NAD(+) kinase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dy6 OCA], [http://pdbe.org/4dy6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dy6 RCSB], [http://www.ebi.ac.uk/pdbsum/4dy6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dy6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NADK1_LISMO NADK1_LISMO]] Involved in the regulation of the intracellular balance of NAD and NADP, and is a key enzyme in the biosynthesis of NADP. Catalyzes specifically the phosphorylation on 2'-hydroxyl of the adenosine moiety of NAD to yield NADP.[HAMAP-Rule:MF_00361]<ref>PMID:17686780</ref> <ref>PMID:22608967</ref> | + | [[https://www.uniprot.org/uniprot/NADK1_LISMO NADK1_LISMO]] Involved in the regulation of the intracellular balance of NAD and NADP, and is a key enzyme in the biosynthesis of NADP. Catalyzes specifically the phosphorylation on 2'-hydroxyl of the adenosine moiety of NAD to yield NADP.[HAMAP-Rule:MF_00361]<ref>PMID:17686780</ref> <ref>PMID:22608967</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacterium monocytogenes hominis nyfeldt 1932]] | + | [[Category: Large Structures]] |
| - | [[Category: Arold, S]] | + | [[Category: Listeria monocytogenes]] |
| - | [[Category: Assairi, L]] | + | [[Category: Arold S]] |
| - | [[Category: Labesse, G]] | + | [[Category: Assairi L]] |
| - | [[Category: Pochet, S]] | + | [[Category: Labesse G]] |
| - | [[Category: Poncet-Montange, G]] | + | [[Category: Pochet S]] |
| - | [[Category: Inorganic polyphosphate]]
| + | [[Category: Poncet-Montange G]] |
| - | [[Category: Lmnadk1]]
| + | |
| - | [[Category: Nad analog]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
[NADK1_LISMO] Involved in the regulation of the intracellular balance of NAD and NADP, and is a key enzyme in the biosynthesis of NADP. Catalyzes specifically the phosphorylation on 2'-hydroxyl of the adenosine moiety of NAD to yield NADP.[HAMAP-Rule:MF_00361][1] [2]
Publication Abstract from PubMed
Here we describe the crystal structures of the NAD kinase (LmNADK1) from Listeria monocytogenes in complex with its substrate NAD, its product NADP, or two synthesized NAD mimics. We identified one of the NAD mimics, di-adenosine diphosphate, as a new substrate for LmNADK1, whereas we showed that the closely related compound di-5'-thioadenosine is a novel non-natural inhibitor for this enzyme. These structures suggest a mechanism involving substrate-assisted catalysis. Indeed, sequence/structure comparison and directed mutagenesis have previously shown that NAD kinases (NADKs) and the distantly related 6-phosphofructokinases share the same catalytically important GGDGT motif. However, in this study we have shown that these enzymes use the central aspartate of this motif differently. Although this acidic residue chelates the catalytic Mg(2+) ion in 6-phosphofructokinases, it activates the phospho-acceptor (NAD) in NADKs. Sequence/structure comparisons suggest that the role of this aspartate would be conserved in NADKs and the related sphingosine and diacylglycerol kinases.
NAD kinases use substrate-assisted catalysis for specific recognition of NAD.,Poncet-Montange G, Assairi L, Arold S, Pochet S, Labesse G J Biol Chem. 2007 Nov 23;282(47):33925-34. Epub 2007 Aug 8. PMID:17686780[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Poncet-Montange G, Assairi L, Arold S, Pochet S, Labesse G. NAD kinases use substrate-assisted catalysis for specific recognition of NAD. J Biol Chem. 2007 Nov 23;282(47):33925-34. Epub 2007 Aug 8. PMID:17686780 doi:10.1074/jbc.M701394200
- ↑ Gelin M, Poncet-Montange G, Assairi L, Morellato L, Huteau V, Dugue L, Dussurget O, Pochet S, Labesse G. Screening and In Situ Synthesis Using Crystals of a NAD Kinase Lead to a Potent Antistaphylococcal Compound. Structure. 2012 May 16. PMID:22608967 doi:10.1016/j.str.2012.03.024
- ↑ Poncet-Montange G, Assairi L, Arold S, Pochet S, Labesse G. NAD kinases use substrate-assisted catalysis for specific recognition of NAD. J Biol Chem. 2007 Nov 23;282(47):33925-34. Epub 2007 Aug 8. PMID:17686780 doi:10.1074/jbc.M701394200
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