6z65: Difference between revisions
New page: '''Unreleased structure''' The entry 6z65 is ON HOLD Authors: Gelin, M., Labesse, G. Description: Crystal structure of NAD kinase 1 from Listeria monocytogenes in complex with a di-ade... |
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==Crystal structure of NAD kinase 1 from Listeria monocytogenes in complex with a di-adenosine derivative== | |||
<StructureSection load='6z65' size='340' side='right'caption='[[6z65]], [[Resolution|resolution]] 1.97Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6z65]] 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=6Z65 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z65 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]] 1.97Å</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=Q9N:~{N}-[[(2~{R},3~{S},4~{R},5~{R})-5-[8-[3-[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy]prop-1-ynyl]-6-azanyl-purin-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl]-4-azanyl-butanamide'>Q9N</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=6z65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z65 OCA], [https://pdbe.org/6z65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z65 RCSB], [https://www.ebi.ac.uk/pdbsum/6z65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z65 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 (NAD) kinases are essential and ubiquitous enzymes involved in the tight regulation of NAD/nicotinamide adenine dinucleotide phosphate (NADP) levels in many metabolic pathways. Consequently, they represent promising therapeutic targets in cancer and antibacterial treatments. We previously reported diadenosine derivatives as NAD kinase inhibitors with bactericidal activities on Staphylococcus aureus. Among them, one compound (namely NKI1) was found effective in vivo in a mouse infection model. With the aim to gain detailed knowledge about the selectivity and mechanism of action of this lead compound, we planned to develop a chemical probe that could be used in affinity-based chemoproteomic approaches. Here, we describe the first functionalized chemical probe targeting a bacterial NAD kinase. Aminoalkyl functional groups were introduced on NKI1 for further covalent coupling to an activated Sepharose(TM) matrix. Inhibitory properties of functionalized NKI1 derivatives together with X-ray characterization of their complexes with the NAD kinase led to identify candidate compounds that are amenable to covalent coupling to a matrix. | |||
New Chemical Probe Targeting Bacterial NAD Kinase.,Clement DA, Leseigneur C, Gelin M, Coelho D, Huteau V, Lionne C, Labesse G, Dussurget O, Pochet S Molecules. 2020 Oct 22;25(21). pii: molecules25214893. doi:, 10.3390/molecules25214893. PMID:33105870<ref>PMID:33105870</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6z65" style="background-color:#fffaf0;"></div> | ||
[[Category: Gelin | |||
==See Also== | |||
*[[NAD kinase|NAD kinase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Listeria monocytogenes EGD-e]] | |||
[[Category: Gelin M]] | |||
[[Category: Labesse G]] | |||
Latest revision as of 16:42, 24 January 2024
Crystal structure of NAD kinase 1 from Listeria monocytogenes in complex with a di-adenosine derivativeCrystal structure of NAD kinase 1 from Listeria monocytogenes in complex with a di-adenosine derivative
Structural highlights
FunctionNADK1_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 PubMedNicotinamide adenine dinucleotide (NAD) kinases are essential and ubiquitous enzymes involved in the tight regulation of NAD/nicotinamide adenine dinucleotide phosphate (NADP) levels in many metabolic pathways. Consequently, they represent promising therapeutic targets in cancer and antibacterial treatments. We previously reported diadenosine derivatives as NAD kinase inhibitors with bactericidal activities on Staphylococcus aureus. Among them, one compound (namely NKI1) was found effective in vivo in a mouse infection model. With the aim to gain detailed knowledge about the selectivity and mechanism of action of this lead compound, we planned to develop a chemical probe that could be used in affinity-based chemoproteomic approaches. Here, we describe the first functionalized chemical probe targeting a bacterial NAD kinase. Aminoalkyl functional groups were introduced on NKI1 for further covalent coupling to an activated Sepharose(TM) matrix. Inhibitory properties of functionalized NKI1 derivatives together with X-ray characterization of their complexes with the NAD kinase led to identify candidate compounds that are amenable to covalent coupling to a matrix. New Chemical Probe Targeting Bacterial NAD Kinase.,Clement DA, Leseigneur C, Gelin M, Coelho D, Huteau V, Lionne C, Labesse G, Dussurget O, Pochet S Molecules. 2020 Oct 22;25(21). pii: molecules25214893. doi:, 10.3390/molecules25214893. PMID:33105870[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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