View source for 7zzf


==Crystal structure of NAD kinase 1 from Listeria monocytogenes in complex with a linear di-adenosine derivative==
<StructureSection load='7zzf' size='340' side='right'caption='[[7zzf]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7zzf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Listeria_monocytogenes_EGD-e Listeria monocytogenes EGD-e]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZZF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.41&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=KHX:(1~{R},23~{R},24~{S},25~{R})-14-[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl]-7-azanyl-24,25-bis(oxidanyl)-26-oxa-2,4,6,9,14,17,21-heptazatetracyclo[21.2.1.0^{2,10}.0^{3,8}]hexacosa-3(8),4,6,9-tetraen-11-yne-18,20-dione'>KHX</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=7zzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zzf OCA], [https://pdbe.org/7zzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zzf RCSB], [https://www.ebi.ac.uk/pdbsum/7zzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zzf ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== Publication Abstract from PubMed ==
Nicotinamide adenine dinucleotide kinases (NAD kinases) are essential and ubiquitous enzymes involved in the production of NADP(H) which is an essential cofactor in many metabolic pathways. Targeting NAD kinase (NADK), a rate limiting enzyme of NADP biosynthesis pathway, represents a new promising approach to treat bacterial infections. Previously, we have produced the first NADK inhibitor active against staphylococcal infection. From this linear di-adenosine derivative, namely NKI1, we designed macrocyclic analogues. Here, we describe the synthesis and evaluation of an original series of cyclic diadenosine derivatives as NADK inhibitors of two pathogenic bacteria, Listeria monocytogenes and Staphylococcus aureus. The nature and length of the link between the two adenosine units were examined leading to sub-micromolar inhibitors of NADK1 from L. monocytogenes, including its most potent in vitro inhibitor reported so far (with a 300-fold improvement compared to NKI1).

Synthesis and structure-activity relationship studies of original cyclic diadenosine derivatives as nanomolar inhibitors of NAD kinase from pathogenic bacteria.,Clement DA, Gelin M, Leseigneur C, Huteau V, Mondange L, Pons JL, Dussurget O, Lionne C, Labesse G, Pochet S Eur J Med Chem. 2023 Jan 15;246:114941. doi: 10.1016/j.ejmech.2022.114941. Epub , 2022 Nov 23. PMID:36455355<ref>PMID:36455355</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7zzf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Listeria monocytogenes EGD-e]]
[[Category: Gelin M]]
[[Category: Labesse G]]