7s04
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==1-deoxy-D-xylulose 5-phosphate reductoisomerase (IspC) from Acinetobacter baumannii in complex with FR900098, NADPH, and a magnesium ion== | ==1-deoxy-D-xylulose 5-phosphate reductoisomerase (IspC) from Acinetobacter baumannii in complex with FR900098, NADPH, and a magnesium ion== | ||
| - | <StructureSection load='7s04' size='340' side='right'caption='[[7s04]]' scene=''> | + | <StructureSection load='7s04' size='340' side='right'caption='[[7s04]], [[Resolution|resolution]] 2.52Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S04 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7s04]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S04 FirstGlance]. <br> |
| - | </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=7s04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s04 OCA], [https://pdbe.org/7s04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s04 RCSB], [https://www.ebi.ac.uk/pdbsum/7s04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s04 ProSAT]</span></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]] 2.52Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F98:3-[ETHANOYL(HYDROXY)AMINO]PROPYLPHOSPHONIC+ACID'>F98</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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=7s04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s04 OCA], [https://pdbe.org/7s04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s04 RCSB], [https://www.ebi.ac.uk/pdbsum/7s04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s04 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DXR_ACIB3 DXR_ACIB3] Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The ESKAPE pathogens comprise a group of multidrug-resistant bacteria that are the leading cause of nosocomial infections worldwide. The prevalence of antibiotic resistant strains and the relative ease by which bacteria acquire resistance genes highlight the continual need for the development of novel antibiotics against new drug targets. The methylerythritol phosphate (MEP) pathway is an attractive target for the development of new antibiotics. The MEP pathway governs the synthesis of isoprenoids, which are key lipid precursors for vital cell components such as ubiquinone and bacterial hopanoids. Additionally, the MEP pathway is entirely distinct from the corresponding mammalian pathway, the mevalonic acid (MVA) pathway, making the first committed enzyme of the MEP pathway, 1-deoxy-d-xylulose 5-phosphate reductoisomerase (IspC), an attractive target for antibiotic development. To facilitate drug development against two of the ESKAPE pathogens, Acinetobacter baumannii and Klebsiella pneumoniae, we cloned, expressed, purified, and characterized IspC from these two Gram-negative bacteria. Enzyme inhibition assays using IspC from these two pathogens, and compounds fosmidomycin and FR900098, indicate IC50 values ranging from 19.5-45.5 nM. Antimicrobial susceptibility tests with these inhibitors reveal that A. baumannii is susceptible to FR900098, whereas K. pneumoniae is susceptible to both compounds. Finally, to facilitate structure-based drug design of inhibitors targeting A. baumannii IspC, we determined the 2.5 A crystal structure of IspC from A. baumannii in complex with inhibitor FR900098, and cofactors NADPH and magnesium. | ||
| + | |||
| + | Characterization and Inhibition of 1-Deoxy-d-Xylulose 5-Phosphate Reductoisomerase: A Promising Drug Target in Acinetobacter baumannii and Klebsiella pneumoniae.,Ball HS, Girma MB, Zainab M, Soojhawon I, Couch RD, Noble SM ACS Infect Dis. 2021 Oct 21. doi: 10.1021/acsinfecdis.1c00132. PMID:34672535<ref>PMID:34672535</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7s04" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[DXP reductoisomerase 3D Structures|DXP reductoisomerase 3D Structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Acinetobacter baumannii]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Ball HS]] | [[Category: Ball HS]] | ||
[[Category: Couch RD]] | [[Category: Couch RD]] | ||
[[Category: Noble SM]] | [[Category: Noble SM]] | ||
Current revision
1-deoxy-D-xylulose 5-phosphate reductoisomerase (IspC) from Acinetobacter baumannii in complex with FR900098, NADPH, and a magnesium ion
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