8er0: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8er0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chryseobacterium_oncorhynchi Chryseobacterium oncorhynchi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ER0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ER0 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8er0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chryseobacterium_oncorhynchi Chryseobacterium oncorhynchi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ER0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ER0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=TDC:5A,6-ANHYDROTETRACYCLINE'>TDC</scene></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]] 2.2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=TDC:5A,6-ANHYDROTETRACYCLINE'>TDC</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=8er0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8er0 OCA], [https://pdbe.org/8er0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8er0 RCSB], [https://www.ebi.ac.uk/pdbsum/8er0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8er0 ProSAT]</span></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=8er0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8er0 OCA], [https://pdbe.org/8er0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8er0 RCSB], [https://www.ebi.ac.uk/pdbsum/8er0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8er0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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</div> | </div> | ||
<div class="pdbe-citations 8er0" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 8er0" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Monooxygenase 3D structures|Monooxygenase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Latest revision as of 13:23, 25 October 2023
X-ray crystal structure of Tet(X6) bound to anhydrotetracyclineX-ray crystal structure of Tet(X6) bound to anhydrotetracycline
Structural highlights
FunctionA0A316WTJ0_9FLAO An FAD-requiring monooxygenase active on some tetracycline antibiotic derivatives, which leads to their inactivation. Hydroxylates carbon 11a of tetracycline and some analogs.[HAMAP-Rule:MF_00845] Publication Abstract from PubMedInactivation of tetracycline antibiotics by tetracycline destructases (TDases) remains a clinical and agricultural threat. TDases can be classified as type 1 Tet(X)-like TDases and type 2 soil-derived TDases. Type 1 TDases are widely identified in clinical pathogens. A combination therapy of tetracycline and a TDase inhibitor is much needed to rescue the clinical efficacy of tetracyclines. Anhydrotetracycline is a pan-TDase inhibitor that inhibits both type 1 and type 2 TDases. Here, we present structural, biochemical, and phenotypic evidence that anhydrotetracycline binds in a substrate-like orientation and competitively inhibits the type 1 TDase Tet(X6) to rescue tetracycline antibiotic activity as a sacrificial substrate. Anhydrotetracycline interacting residues of Tet(X6) are conserved within type 1 TDases, indicating a conserved binding mode and mechanism of inhibition. This mode of binding and inhibition is distinct from anhydrotetracycline's inhibition of type 2 TDases. This study forms the framework for development of next-generation therapies to counteract enzymatic tetracycline resistance. Structure of anhydrotetracycline-bound Tet(X6) reveals the mechanism for inhibition of type 1 tetracycline destructases.,Kumar H, Williford EE, Blake KS, Virgin-Downey B, Dantas G, Wencewicz TA, Tolia NH Commun Biol. 2023 Apr 17;6(1):423. doi: 10.1038/s42003-023-04792-4. PMID:37062778[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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