View source for 5wew


==Crystal structure of Klebsiella pneumoniae fosfomycin resistance protein (FosAKP) with inhibitor (ANY1) bound==
<StructureSection load='5wew' size='340' side='right'caption='[[5wew]], [[Resolution|resolution]] 3.18&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5wew]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae_30684/NJST258_2 Klebsiella pneumoniae 30684/NJST258_2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WEW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WEW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.178&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A81:6,6-(4-nitro-1H-pyrazole-3,5-diyl)bis(3-bromopyrazolo[1,5-a]pyrimidin-2(1H)-one)'>A81</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=5wew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wew OCA], [https://pdbe.org/5wew PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wew RCSB], [https://www.ebi.ac.uk/pdbsum/5wew PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wew ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/W8UNW6_KLEPN W8UNW6_KLEPN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The spread of multidrug or extensively drug-resistant Gram-negative bacteria is a serious public health issue. There are too few new antibiotics in development to combat the threat of multidrug-resistant infections, and consequently the rate of increasing antibiotic resistance is outpacing the drug development process. This fundamentally threatens our ability to treat common infectious diseases. Fosfomycin (FOM) has an established track record of safety in humans and is highly active against Escherichia coli, including multidrug-resistant strains. However, many other Gram-negative pathogens, including the "priority pathogens" Klebsiella pneumoniae and Pseudomonas aeruginosa, are inherently resistant to FOM due to the chromosomally-encoded fosA gene, which directs expression of a metal-dependent glutathione S-transferase (FosA) that metabolizes FOM. In this study, we describe the discovery and biochemical and structural characterization of 3-bromo-6-[3-(3-bromo-2-oxo-1H-pyrazolo[1,5-a]pyrimidin-6-yl)-4-nitro-1H-pyrazol- 5-yl]-1H-pyrazolo[1,5-a]pyrimidin-2-one (ANY1), a small molecule active site inhibitor of FosA. Importantly, ANY1 potentiates FOM activity in representative Gram-negative pathogens. Collectively, our study outlines a new strategy to expand FOM activity to a broader spectrum of Gram-negative pathogens, including multidrug-resistant strains.

Small molecule inhibitor of FosA expands fosfomycin activity to multidrug-resistant Gram-negative pathogens.,Tomich AD, Klontz EH, Deredge D, Barnard JP, McElheny CL, Eshbach ML, Weisz OA, Wintrode P, Doi Y, Sundberg EJ, Sluis-Cremer N Antimicrob Agents Chemother. 2019 Jan 14. pii: AAC.01524-18. doi:, 10.1128/AAC.01524-18. PMID:30642934<ref>PMID:30642934</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5wew" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Klebsiella pneumoniae 30684/NJST258_2]]
[[Category: Large Structures]]
[[Category: Klontz EH]]
[[Category: Sundberg EJ]]