View source for 4nb1


==Crystal Structure of FosB from Staphylococcus aureus at 1.80 Angstrom Resolution with L-Cysteine-Cys9 Disulfide==
<StructureSection load='4nb1' size='340' side='right'caption='[[4nb1]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4nb1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_N315 Staphylococcus aureus subsp. aureus N315]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NB1 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4nb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nb1 OCA], [https://pdbe.org/4nb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nb1 RCSB], [https://www.ebi.ac.uk/pdbsum/4nb1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nb1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FOSB_STAAN FOSB_STAAN] 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 global morbidity and mortality. Like many multi-drug-resistant organisms, S. aureus contains antibiotic-modifying enzymes that facilitate resistance to a multitude of antimicrobial compounds. FosB is a Mn(2+)-dependent fosfomycin-inactivating enzyme found in S. aureus that catalyzes nucleophilic addition of either l-cysteine (l-Cys) or bacillithiol (BSH) to the antibiotic, resulting in a modified compound with no bactericidal properties. The three-dimensional X-ray crystal structure of FosB from S. aureus (FosB(Sa)) has been determined to a resolution of 1.15 A. Cocrystallization of FosB(Sa) with either l-Cys or BSH results in a disulfide bond between the exogenous thiol and the active site Cys9 of the enzyme. An analysis of the structures suggests that a highly conserved loop region of the FosB enzymes must change conformation to bind fosfomycin. While two crystals of FosB(Sa) contain Zn(2+) in the active site, kinetic analyses of FosB(Sa) indicated that the enzyme is inhibited by Zn(2+) for l-Cys transferase activity and only marginally active for BSH transferase activity. Fosfomycin-treated disk diffusion assays involving S. aureus Newman and the USA300 JE2 methicillin-resistant S. aureus demonstrate a marked increase in the sensitivity of the organism to the antibiotic in either the BSH or FosB null strains, indicating that both are required for survival of the organism in the presence of the antibiotic. This work identifies FosB as a primary fosfomycin-modifying pathway of S. aureus and establishes the enzyme as a potential therapeutic target for increased efficacy of fosfomycin against the pathogen.

Structure and Function of the Genomically Encoded Fosfomycin Resistance Enzyme, FosB, from Staphylococcus aureus.,Thompson MK, Keithly ME, Goodman MC, Hammer ND, Cook PD, Jagessar KL, Harp J, Skaar EP, Armstrong RN Biochemistry. 2014 Feb 4;53(4):755-65. doi: 10.1021/bi4015852. Epub 2014 Jan 21. PMID:24447055<ref>PMID:24447055</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4nb1" style="background-color:#fffaf0;"></div>

==See Also==
*[[Metallothiol transferase FosB|Metallothiol transferase FosB]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus subsp. aureus N315]]
[[Category: Armstrong RN]]
[[Category: Cook PD]]
[[Category: Goodman MC]]
[[Category: Harp J]]
[[Category: Jagessar K]]
[[Category: Keithly ME]]
[[Category: Thompson MK]]