This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
8er0
From Proteopedia
(Difference between revisions)
| (One intermediate revision not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==X-ray crystal structure of Tet(X6) bound to anhydrotetracycline== | |
| + | <StructureSection load='8er0' size='340' side='right'caption='[[8er0]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| + | == 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> | ||
| + | </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> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A0A316WTJ0_9FLAO A0A316WTJ0_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] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Inactivation 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<ref>PMID:37062778</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8er0" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Monooxygenase 3D structures|Monooxygenase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Chryseobacterium oncorhynchi]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Kumar H]] | ||
| + | [[Category: Tolia NH]] | ||
Current revision
X-ray crystal structure of Tet(X6) bound to anhydrotetracycline
| |||||||||||
