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| | <StructureSection load='3e27' size='340' side='right'caption='[[3e27]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='3e27' size='340' side='right'caption='[[3e27]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3e27]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_cereus_var._anthracis"_(cohn_1872)_smith_et_al._1946 "bacillus cereus var. anthracis" (cohn 1872) smith et al. 1946]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E27 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E27 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3e27]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E27 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E27 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DND:NICOTINIC+ACID+ADENINE+DINUCLEOTIDE'>DND</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">nadD, BT9727_4068 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 "Bacillus cereus var. anthracis" (Cohn 1872) Smith et al. 1946])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DND:NICOTINIC+ACID+ADENINE+DINUCLEOTIDE'>DND</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Nicotinate-nucleotide_adenylyltransferase Nicotinate-nucleotide adenylyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.18 2.7.7.18] </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=3e27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e27 OCA], [https://pdbe.org/3e27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e27 RCSB], [https://www.ebi.ac.uk/pdbsum/3e27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e27 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=3e27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e27 OCA], [https://pdbe.org/3e27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e27 RCSB], [https://www.ebi.ac.uk/pdbsum/3e27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e27 ProSAT]</span></td></tr> |
| | </table> | | </table> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Bacillus anthracis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Nicotinate-nucleotide adenylyltransferase]]
| + | [[Category: Eyobo Y]] |
| - | [[Category: Eyobo, Y]] | + | [[Category: Martynowski D]] |
| - | [[Category: Martynowski, D]] | + | [[Category: Zhang H]] |
| - | [[Category: Zhang, H]] | + | |
| - | [[Category: Nucleotide-binding motif]]
| + | |
| - | [[Category: Nucleotidyltransferase]]
| + | |
| - | [[Category: Rossman-like fold]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The emergence of multidrug-resistant pathogens necessitates the search for new antibiotics acting on previously unexplored targets. Nicotinate mononucleotide adenylyltransferase of the NadD family, an essential enzyme of NAD biosynthesis in most bacteria, was selected as a target for structure-based inhibitor development. Using iterative in silico and in vitro screens, we identified small molecule compounds that efficiently inhibited target enzymes from Escherichia coli (ecNadD) and Bacillus anthracis (baNadD) but had no effect on functionally equivalent human enzymes. On-target antibacterial activity was demonstrated for some of the selected inhibitors. A 3D structure of baNadD was solved in complex with one of these inhibitors (3_02), providing mechanistic insights and guidelines for further improvement. Most importantly, the results of this study help validate NadD as a target for the development of antibacterial agents with potential broad-spectrum activity.
Targeting NAD biosynthesis in bacterial pathogens: Structure-based development of inhibitors of nicotinate mononucleotide adenylyltransferase NadD.,Sorci L, Pan Y, Eyobo Y, Rodionova I, Huang N, Kurnasov O, Zhong S, MacKerell AD Jr, Zhang H, Osterman AL Chem Biol. 2009 Aug 28;16(8):849-61. PMID:19716475[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sorci L, Pan Y, Eyobo Y, Rodionova I, Huang N, Kurnasov O, Zhong S, MacKerell AD Jr, Zhang H, Osterman AL. Targeting NAD biosynthesis in bacterial pathogens: Structure-based development of inhibitors of nicotinate mononucleotide adenylyltransferase NadD. Chem Biol. 2009 Aug 28;16(8):849-61. PMID:19716475 doi:10.1016/j.chembiol.2009.07.006
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