3v8p: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3v8p]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacterium_monocytogenes_hominis"_nyfeldt_1932 "bacterium monocytogenes hominis" nyfeldt 1932]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V8P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3V8P FirstGlance]. <br> | <table><tr><td colspan='2'>[[3v8p]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacterium_monocytogenes_hominis"_nyfeldt_1932 "bacterium monocytogenes hominis" nyfeldt 1932]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V8P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3V8P FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=ZNB:2-[6- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=ZNB:2-[6-azanyl-9-[(2R,3R,4S,5R)-5-[[(azanylidene-$l^{4}-azanylidene)amino]methyl]-3,4-bis(oxidanyl)oxolan-2-yl]purin-8-yl]sulfanyl-N-[[(2R,3S,4R,5R)-5-(6-azanyl-8-bromanyl-purin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl]ethanamide'>ZNB</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2i2c|2i2c]], [[3v7v|3v7v]], [[3v7w|3v7w]], [[3v7y|3v7y]], [[3v80|3v80]], [[3v8m|3v8m]], [[3v8n|3v8n]], [[3v8q|3v8q]], [[3v8r|3v8r]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2i2c|2i2c]], [[3v7v|3v7v]], [[3v7w|3v7w]], [[3v7y|3v7y]], [[3v80|3v80]], [[3v8m|3v8m]], [[3v8n|3v8n]], [[3v8q|3v8q]], [[3v8r|3v8r]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ppnK1, lmo0968 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1639 "Bacterium monocytogenes hominis" Nyfeldt 1932])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ppnK1, lmo0968 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1639 "Bacterium monocytogenes hominis" Nyfeldt 1932])</td></tr> | ||
Revision as of 13:14, 8 November 2017
Crystal structure of NAD kinase 1 from Listeria monocytogenes in complex with a new di-adenosine inhibitor formed in situCrystal structure of NAD kinase 1 from Listeria monocytogenes in complex with a new di-adenosine inhibitor formed in situ
Structural highlights
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 PubMedMaking 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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