View source for 6rgb


==Crystal structure of NAD kinase 1 from Listeria monocytogenes in complexe with an inhibitor==
<StructureSection load='6rgb' size='340' side='right'caption='[[6rgb]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rgb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RGB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RGB 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=K38:(2~{R},3~{R},4~{S},5~{R})-2-(6-aminopurin-9-yl)-5-[[3-[6-azanyl-9-[(2~{R},3~{R},4~{S},5~{R})-5-(hydroxymethyl)-3,4-bis(oxidanyl)oxolan-2-yl]purin-8-yl]prop-2-ynylamino]methyl]oxolane-3,4-diol'>K38</scene></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=6rgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rgb OCA], [http://pdbe.org/6rgb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rgb RCSB], [http://www.ebi.ac.uk/pdbsum/6rgb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rgb 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 6rgb" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Gelin, M]]
[[Category: Labesse, G]]
[[Category: Tetrameric nad kinase]]
[[Category: Transferase]]