View source for 6rg6


==Crystal structure of NAD kinase 1 from Listeria monocytogenes in complexe with an inhibitor==
<StructureSection load='6rg6' size='340' side='right'caption='[[6rg6]], [[Resolution|resolution]] 2.52&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rg6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lismo Lismo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RG6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RG6 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=K3B:(2~{R},3~{R},4~{S},5~{R})-2-(6-aminopurin-9-yl)-5-[3-(6-azanyl-9~{H}-purin-8-yl)prop-2-ynoxymethyl]oxolane-3,4-diol'>K3B</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">nadK1, lmo0968 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=169963 LISMO])</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=6rg6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rg6 OCA], [http://pdbe.org/6rg6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rg6 RCSB], [http://www.ebi.ac.uk/pdbsum/6rg6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rg6 ProSAT]</span></td></tr>
</table>
== 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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Antibiotic resistance is a worldwide threat due to the decreasing supply of new antimicrobials. Novel targets and innovative strategies are urgently needed to generate pathbreaking drug compounds. NAD kinase (NADK) is essential for growth in most bacteria, as it supports critical metabolic pathways. Here, we report the discovery of a new class of antibacterials that targets bacterial NADK. We generated a series of small synthetic adenine derivatives to screen those harboring promising substituents in order to guide efficient fragment linking. This led to NKI1, a new lead compound inhibiting NADK that showed in vitro bactericidal activity against Staphylococcus aureus. In a murine model of infection, NKI1 restricted survival of the bacteria, including methicillin-resistant S. aureus. Collectively, these findings identify bacterial NADK as a potential drug target and NKI1 as a lead compound in the treatment of staphylococcal infections.

From Substrate to Fragments to Inhibitor Active In Vivo against Staphylococcus aureus.,Gelin M, Paoletti J, Nahori MA, Huteau V, Leseigneur C, Jouvion G, Dugue L, Clement D, Pons JL, Assairi L, Pochet S, Labesse G, Dussurget O ACS Infect Dis. 2020 Feb 14. doi: 10.1021/acsinfecdis.9b00368. PMID:32017533<ref>PMID:32017533</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rg6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Lismo]]
[[Category: Gelin, M]]
[[Category: Labesse, G]]
[[Category: Tetrameric nad kinase]]
[[Category: Transferase]]