4a6n
From Proteopedia
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| - | + | ==STRUCTURE OF THE TETRACYCLINE DEGRADING MONOOXYGENASE TETX IN COMPLEX WITH TIGECYCLINE== | |
| - | + | <StructureSection load='4a6n' size='340' side='right' caption='[[4a6n]], [[Resolution|resolution]] 2.30Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[4a6n]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron Bacteroides thetaiotaomicron]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A6N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A6N FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=T1C:TIGECYCLINE'>T1C</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xdo|2xdo]], [[2xyo|2xyo]], [[2y6q|2y6q]], [[2y6r|2y6r]], [[4a99|4a99]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4a6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a6n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a6n RCSB], [http://www.ebi.ac.uk/pdbsum/4a6n PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Expression of the aromatic hydroxylase TetX under aerobic conditions confers bacterial resistance against tetracycline antibiotics. Hydroxylation inactivates and degrades tetracyclines, preventing inhibition of the prokaryotic ribosome. X-ray crystal structure analyses of TetX in complex with the second-generation and third-generation tetracyclines minocycline and tigecycline at 2.18 and 2.30 A resolution, respectively, explain why both clinically potent antibiotics are suitable substrates. Both tetracyclines bind in a large tunnel-shaped active site in close contact to the cofactor FAD, pre-oriented for regioselective hydroxylation to 11a-hydroxytetracyclines. The characteristic bulky 9-tert-butylglycylamido substituent of tigecycline is solvent-exposed and does not interfere with TetX binding. In the TetX-minocycline complex a second binding site for a minocycline dimer is observed close to the active-site entrance. The pocket is formed by the crystal packing arrangement on the surface of two neighbouring TetX monomers. Crystal structure analysis at 2.73 A resolution of xenon-pressurized TetX identified two adjacent Xe-binding sites. These putative dioxygen-binding cavities are located in the substrate-binding domain next to the active site. Molecular-dynamics simulations were performed in order to characterize dioxygen-diffusion pathways to FADH2 at the active site. | ||
| - | + | Putative dioxygen-binding sites and recognition of tigecycline and minocycline in the tetracycline-degrading monooxygenase TetX.,Volkers G, Damas JM, Palm GJ, Panjikar S, Soares CM, Hinrichs W Acta Crystallogr D Biol Crystallogr. 2013 Sep 1;69(Pt 9):1758-67. doi:, 10.1107/S0907444913013802. Epub 2013 Aug 15. PMID:23999299<ref>PMID:23999299</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Bacteroides thetaiotaomicron]] | [[Category: Bacteroides thetaiotaomicron]] | ||
| - | [[Category: Hinrichs, W | + | [[Category: Hinrichs, W]] |
| - | [[Category: Palm, G J | + | [[Category: Palm, G J]] |
| - | [[Category: Volkers, G | + | [[Category: Volkers, G]] |
| - | [[Category: Weiss, M S | + | [[Category: Weiss, M S]] |
[[Category: Antibiotic resistance]] | [[Category: Antibiotic resistance]] | ||
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
Revision as of 09:37, 21 December 2014
STRUCTURE OF THE TETRACYCLINE DEGRADING MONOOXYGENASE TETX IN COMPLEX WITH TIGECYCLINE
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