7qvs: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7qvs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QVS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QVS FirstGlance]. <br>
<table><tr><td colspan='2'>[[7qvs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QVS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QVS FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7qvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qvs OCA], [https://pdbe.org/7qvs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qvs RCSB], [https://www.ebi.ac.uk/pdbsum/7qvs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qvs 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=7qvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qvs OCA], [https://pdbe.org/7qvs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qvs RCSB], [https://www.ebi.ac.uk/pdbsum/7qvs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qvs ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/A0A071KS55_PSEAI A0A071KS55_PSEAI] 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]
[https://www.uniprot.org/uniprot/A0A071KS55_PSEAI A0A071KS55_PSEAI] 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]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Multidrug resistance is a major public health problem that requires the urgent development of new antibiotics and therefore the identification of novel bacterial targets. The activity of nicotinamide adenine dinucleotide kinase, NADK, is essential in all bacteria tested so far, including many human pathogens that display antibiotic resistance leading to the failure of current treatments. Inhibiting NADK is therefore a promising and innovative antibacterial strategy since there is currently no drug on the market targeting this enzyme. Through a fragment-based drug design approach, we have recently developed a NAD(+) -competitive inhibitor of NADKs, which displayed in vivo activity against Staphylococcus aureus. Here, we show that this compound, a di-adenosine derivative, is inactive against the NADK enzyme from the Gram-negative bacteria Pseudomonas aeruginosa (PaNADK). This lack of activity can be explained by the crystal structure of PaNADK, which was determined in complex with NADP(+) in this study. Structural analysis led us to design and synthesize a benzamide adenine dinucleoside analogue, active against PaNADK. This novel compound efficiently inhibited PaNADK enzymatic activity in vitro with a Ki of 4.6 mum. Moreover, this compound reduced P. aeruginosa infection in vivo in a zebrafish model.


Structure-based design, synthesis and biological evaluation of a NAD(+) analogue targeting Pseudomonas aeruginosa NAD kinase.,Rahimova R, Nogaret P, Huteau V, Gelin M, Clement DA, Labesse G, Pochet S, Blanc-Potard AB, Lionne C FEBS J. 2022 Aug 29. doi: 10.1111/febs.16604. PMID:36036789<ref>PMID:36036789</ref>
==See Also==
 
*[[NAD kinase|NAD kinase]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7qvs" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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__TOC__
</StructureSection>
</StructureSection>

Latest revision as of 10:58, 7 February 2024

Pseudomonas aeruginosa nicotinamide adenine dinucleotide kinase (NADK) structure in complex with NADPPseudomonas aeruginosa nicotinamide adenine dinucleotide kinase (NADK) structure in complex with NADP

Structural highlights

7qvs is a 2 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A071KS55_PSEAI 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]

See Also

7qvs, resolution 2.30Å

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