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==Crystal Structure of FosB from Bacillus cereus with Zinc and Phosphonoformate==
<StructureSection load='8dtd' size='340' side='right'caption='[[8dtd]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8dtd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_cereus_ATCC_10987 Bacillus cereus ATCC 10987]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DTD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DTD 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]] 1.95&#8491;</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=8dtd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dtd OCA], [https://pdbe.org/8dtd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dtd RCSB], [https://www.ebi.ac.uk/pdbsum/8dtd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dtd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FOSB_BACC1 FOSB_BACC1] Metallothiol transferase which confers resistance to fosfomycin by catalyzing the addition of a thiol cofactor to fosfomycin. L-cysteine is probably the physiological thiol donor (By similarity).
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== Publication Abstract from PubMed ==
The Gram-positive pathogen Staphylococcus aureus is a leading cause of antimicrobial resistance related deaths worldwide. Like many pathogens with multidrug-resistant strains, S. aureus contains enzymes that confer resistance through antibiotic modification(s). One such enzyme present in S. aureus is FosB, a Mn(2+)-dependent l-cysteine or bacillithiol (BSH) transferase that inactivates the antibiotic fosfomycin. fosB gene knockout experiments show that the minimum inhibitory concentration (MIC) of fosfomycin is significantly reduced when the FosB enzyme is not present. This suggests that inhibition of FosB could be an effective method to restore fosfomycin activity. We used high-throughput in silico-based screening to identify small-molecule analogues of fosfomycin that inhibited thiol transferase activity. Phosphonoformate (PPF) was a top hit from our approach. Herein, we have characterized PPF as a competitive inhibitor of FosB from S. aureus (FosB(Sa)) and Bacillus cereus (FosB(Bc)). In addition, we have determined a crystal structure of FosB(Bc) with PPF bound in the active site. Our results will be useful for future structure-based development of FosB inhibitors that can be delivered in combination with fosfomycin in order to increase the efficacy of this antibiotic.

Inhibition of Fosfomycin Resistance Protein FosB from Gram-Positive Pathogens by Phosphonoformate.,Travis S, Green KD, Gilbert NC, Tsodikov OV, Garneau-Tsodikova S, Thompson MK Biochemistry. 2023 Jan 3;62(1):109-117. doi: 10.1021/acs.biochem.2c00566. Epub , 2022 Dec 16. PMID:36525630<ref>PMID:36525630</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Bacillus cereus ATCC 10987]]
[[Category: Large Structures]]
[[Category: Gilbert NC]]
[[Category: Thompson MK]]
[[Category: Travis S]]