5vqb: Difference between revisions
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The | ==Crystal structure of rifampin monooxygenase from Streptomyces venezuelae, complex with FAD== | ||
<StructureSection load='5vqb' size='340' side='right'caption='[[5vqb]], [[Resolution|resolution]] 3.39Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5vqb]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_venezuelae_ATCC_10712 Streptomyces venezuelae ATCC 10712]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VQB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VQB 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]] 3.391Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5vqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vqb OCA], [https://pdbe.org/5vqb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vqb RCSB], [https://www.ebi.ac.uk/pdbsum/5vqb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vqb ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ROX_STRVP ROX_STRVP] Monooxygenase that can modify rifampicin, thereby inactivating its antibiotic activity (PubMed:29398560). Inactivates a broad range of rifamycin antibiotics (PubMed:29398560).<ref>PMID:29398560</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Rifamycin monooxygenases (Rox) are present in a variety of environmental bacteria and are associated with decomposition of the clinically utilized antibiotic rifampin. Here we report the structure and function of a drug-inducible rox gene from Streptomyces venezuelae, which encodes a class A flavoprotein monooxygenase that inactivates a broad range of rifamycin antibiotics. Our findings describe a mechanism of rifamycin inactivation initiated by monooxygenation of the 2-position of the naphthyl group, which subsequently results in ring opening and linearization of the antibiotic. The result is an antibiotic that no longer adopts the basket-like structure essential for binding to the RNA exit tunnel of the target RpoB, thereby providing the molecular logic of resistance. This unique mechanism of enzymatic inactivation underpins the broad spectrum of rifamycin resistance mediated by Rox enzymes and presents a new antibiotic resistance mechanism not yet seen in microbial antibiotic detoxification. | |||
Rox, a Rifamycin Resistance Enzyme with an Unprecedented Mechanism of Action.,Koteva K, Cox G, Kelso JK, Surette MD, Zubyk HL, Ejim L, Stogios P, Savchenko A, Sorensen D, Wright GD Cell Chem Biol. 2018 Jan 26. pii: S2451-9456(18)30031-X. doi:, 10.1016/j.chembiol.2018.01.009. PMID:29398560<ref>PMID:29398560</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5vqb" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Monooxygenase 3D structures|Monooxygenase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Streptomyces venezuelae ATCC 10712]] | |||
[[Category: Anderson WF]] | |||
[[Category: Cox G]] | |||
[[Category: Kelso J]] | |||
[[Category: Savchenko A]] | |||
[[Category: Stogios PJ]] | |||
[[Category: Wright GD]] | |||
Latest revision as of 16:55, 4 October 2023
Crystal structure of rifampin monooxygenase from Streptomyces venezuelae, complex with FADCrystal structure of rifampin monooxygenase from Streptomyces venezuelae, complex with FAD
Structural highlights
FunctionROX_STRVP Monooxygenase that can modify rifampicin, thereby inactivating its antibiotic activity (PubMed:29398560). Inactivates a broad range of rifamycin antibiotics (PubMed:29398560).[1] Publication Abstract from PubMedRifamycin monooxygenases (Rox) are present in a variety of environmental bacteria and are associated with decomposition of the clinically utilized antibiotic rifampin. Here we report the structure and function of a drug-inducible rox gene from Streptomyces venezuelae, which encodes a class A flavoprotein monooxygenase that inactivates a broad range of rifamycin antibiotics. Our findings describe a mechanism of rifamycin inactivation initiated by monooxygenation of the 2-position of the naphthyl group, which subsequently results in ring opening and linearization of the antibiotic. The result is an antibiotic that no longer adopts the basket-like structure essential for binding to the RNA exit tunnel of the target RpoB, thereby providing the molecular logic of resistance. This unique mechanism of enzymatic inactivation underpins the broad spectrum of rifamycin resistance mediated by Rox enzymes and presents a new antibiotic resistance mechanism not yet seen in microbial antibiotic detoxification. Rox, a Rifamycin Resistance Enzyme with an Unprecedented Mechanism of Action.,Koteva K, Cox G, Kelso JK, Surette MD, Zubyk HL, Ejim L, Stogios P, Savchenko A, Sorensen D, Wright GD Cell Chem Biol. 2018 Jan 26. pii: S2451-9456(18)30031-X. doi:, 10.1016/j.chembiol.2018.01.009. PMID:29398560[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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