6z64

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

6z64 is a 1 chain structure with sequence from Listeria monocytogenes EGD-e. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.89Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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]^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Poncet-Montange G, Assairi L, Arold S, Pochet S, Labesse G. NAD kinases use substrate-assisted catalysis for specific recognition of NAD. J Biol Chem. 2007 Nov 23;282(47):33925-34. Epub 2007 Aug 8. PMID:17686780 doi:10.1074/jbc.M701394200
↑ Gelin M, Poncet-Montange G, Assairi L, Morellato L, Huteau V, Dugue L, Dussurget O, Pochet S, Labesse G. Screening and In Situ Synthesis Using Crystals of a NAD Kinase Lead to a Potent Antistaphylococcal Compound. Structure. 2012 May 16. PMID:22608967 doi:10.1016/j.str.2012.03.024
↑ Clément DA, Leseigneur C, Gelin M, Coelho D, Huteau V, Lionne C, Labesse G, Dussurget O, Pochet S. New Chemical Probe Targeting Bacterial NAD Kinase. Molecules. 2020 Oct 22;25(21):4893. PMID:33105870 doi:10.3390/molecules25214893

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Poncet-Montange G, Assairi L, Arold S, Pochet S, Labesse G. NAD kinases use substrate-assisted catalysis for specific recognition of NAD. J Biol Chem. 2007 Nov 23;282(47):33925-34. Epub 2007 Aug 8. PMID:17686780 doi:10.1074/jbc.M701394200

[2] Gelin M, Poncet-Montange G, Assairi L, Morellato L, Huteau V, Dugue L, Dussurget O, Pochet S, Labesse G. Screening and In Situ Synthesis Using Crystals of a NAD Kinase Lead to a Potent Antistaphylococcal Compound. Structure. 2012 May 16. PMID:22608967 doi:10.1016/j.str.2012.03.024

[3] Clément DA, Leseigneur C, Gelin M, Coelho D, Huteau V, Lionne C, Labesse G, Dussurget O, Pochet S. New Chemical Probe Targeting Bacterial NAD Kinase. Molecules. 2020 Oct 22;25(21):4893. PMID:33105870 doi:10.3390/molecules25214893

[1]

[2]

[3]