3v8p | pdb_00003v8p

Crystal structure of NAD kinase 1 from Listeria monocytogenes in complex with a new di-adenosine inhibitor formed in situ

spinqualitylabelsall models 3v8p, resolution 2.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3v8p is a 1 chain structure with sequence from Listeria monocytogenes. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CIT, ZNB Related: 2i2c, 3v7v, 3v7w, 3v7y, 3v80, 3v8m, 3v8n, 3v8q, 3v8r Gene: ppnK1, lmo0968 (Listeria monocytogenes) Activity: NAD(+) kinase, with EC number 2.7.1.23 Resources: FirstGlance, OCA, RCSB, PDBsum Function [PPNK1_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. Publication Abstract from PubMed Making new ligands for a given protein by in situ ligation of building blocks (or fragments) is an attractive method. However, it suffers from inherent limitations, such as the limited number of available chemical reactions and the low information content of usual chemical library deconvolution. Here, we describe a focused screening of adenosine derivatives using X-ray crystallography. We discovered an unexpected and biocompatible chemical reactivity and have simultaneously identified the mode of binding of the resulting products. We observed that the NAD kinase from Listeria monocytogenes (LmNADK1) can promote amide formation between 5'-amino-5'-deoxyadenosine and carboxylic acid groups. This unexpected reactivity allowed us to bridge in situ two adenosine derivatives to fully occupy the active NAD site. This guided the design of a close analog showing micromolar inhibition of two human pathogenic NAD kinases and potent bactericidal activity against Staphylococcus aureus in vitro. Screening and In Situ Synthesis Using Crystals of a NAD Kinase Lead to a Potent Antistaphylococcal Compound.,Gelin M, Poncet-Montange G, Assairi L, Morellato L, Huteau V, Dugue L, Dussurget O, Pochet S, Labesse G Structure. 2012 May 16. PMID:22608967 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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