View source for 8twg


==Crystal structure of tetracycline destructase Tet(56-2)==
<StructureSection load='8twg' size='340' side='right'caption='[[8twg]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8twg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Legionella_clemsonensis Legionella clemsonensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8TWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TWG 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=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=8twg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8twg OCA], [https://pdbe.org/8twg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8twg RCSB], [https://www.ebi.ac.uk/pdbsum/8twg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8twg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A222NYA8_9GAMM A0A222NYA8_9GAMM] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tetracycline destructases (TDases) are flavin monooxygenases which can confer resistance to all generations of tetracycline antibiotics. The recent increase in the number and diversity of reported TDase sequences enables a deep investigation of the TDase sequence-structure-function landscape. Here, we evaluate the sequence determinants of TDase function through two complementary approaches: (1) constructing profile hidden Markov models to predict new TDases, and (2) using multiple sequence alignments to identify conserved positions important to protein function. Using the HMM-based approach we screened 50 high-scoring candidate sequences in Escherichia coli, leading to the discovery of 13 new TDases. The X-ray crystal structures of two new enzymes from Legionella species were determined, and the ability of anhydrotetracycline to inhibit their tetracycline-inactivating activity was confirmed. Using the MSA-based approach we identified 31 amino acid positions 100% conserved across all known TDase sequences. The roles of these positions were analyzed by alanine-scanning mutagenesis in two TDases, to study the impact on cell and in vitro activity, structure, and stability. These results expand the diversity of TDase sequences and provide valuable insights into the roles of important residues in TDases, and flavin monooxygenases more broadly.

Sequence-structure-function characterization of the emerging tetracycline destructase family of antibiotic resistance enzymes.,Blake KS, Kumar H, Loganathan A, Williford EE, Diorio-Toth L, Xue YP, Tang WK, Campbell TP, Chong DD, Angtuaco S, Wencewicz TA, Tolia NH, Dantas G Commun Biol. 2024 Mar 16;7(1):336. doi: 10.1038/s42003-024-06023-w. PMID:38493211<ref>PMID:38493211</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8twg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Legionella clemsonensis]]
[[Category: Kumar H]]
[[Category: Tang WK]]
[[Category: Tolia N]]