5igr: Difference between revisions
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<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=5igr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5igr OCA], [http://pdbe.org/5igr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5igr RCSB], [http://www.ebi.ac.uk/pdbsum/5igr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5igr ProSAT]</span></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=5igr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5igr OCA], [http://pdbe.org/5igr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5igr RCSB], [http://www.ebi.ac.uk/pdbsum/5igr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5igr ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The macrolides are a class of antibiotic, characterized by a large macrocyclic lactone ring that can be inactivated by macrolide phosphotransferase enzymes. We present structures for MPH(2')-I and MPH(2')-II in the apo state, and in complex with GTP analogs and six different macrolides. These represent the first structures from the two main classes of macrolide phosphotransferases. The structures show that the enzymes are related to the aminoglycoside phosphotransferases, but are distinguished from them by the presence of a large interdomain linker that contributes to an expanded antibiotic binding pocket. This pocket is largely hydrophobic, with a negatively charged patch located at a conserved aspartate residue, rationalizing the broad-spectrum resistance conferred by the enzymes. Complementary mutation studies provide insights into factors governing substrate specificity. A comparison with macrolides bound to their natural target, the 50S ribosome, suggests avenues for next-generation antibiotic development. | |||
Structural Basis for Kinase-Mediated Macrolide Antibiotic Resistance.,Fong DH, Burk DL, Blanchet J, Yan AY, Berghuis AM Structure. 2017 May 2;25(5):750-761.e5. doi: 10.1016/j.str.2017.03.007. Epub 2017, Apr 13. PMID:28416110<ref>PMID:28416110</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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<div class="pdbe-citations 5igr" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 09:20, 4 May 2017
Macrolide 2'-phosphotransferase type I - complex with GDP and oleandomycinMacrolide 2'-phosphotransferase type I - complex with GDP and oleandomycin
Structural highlights
Publication Abstract from PubMedThe macrolides are a class of antibiotic, characterized by a large macrocyclic lactone ring that can be inactivated by macrolide phosphotransferase enzymes. We present structures for MPH(2')-I and MPH(2')-II in the apo state, and in complex with GTP analogs and six different macrolides. These represent the first structures from the two main classes of macrolide phosphotransferases. The structures show that the enzymes are related to the aminoglycoside phosphotransferases, but are distinguished from them by the presence of a large interdomain linker that contributes to an expanded antibiotic binding pocket. This pocket is largely hydrophobic, with a negatively charged patch located at a conserved aspartate residue, rationalizing the broad-spectrum resistance conferred by the enzymes. Complementary mutation studies provide insights into factors governing substrate specificity. A comparison with macrolides bound to their natural target, the 50S ribosome, suggests avenues for next-generation antibiotic development. Structural Basis for Kinase-Mediated Macrolide Antibiotic Resistance.,Fong DH, Burk DL, Blanchet J, Yan AY, Berghuis AM Structure. 2017 May 2;25(5):750-761.e5. doi: 10.1016/j.str.2017.03.007. Epub 2017, Apr 13. PMID:28416110[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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