5ih1

<StructureSection load='5ih1' size='340' side='right' caption='[[5ih1]], [[Resolution|resolution]] 1.31&Aring;' scene=''>

<table><tr><td colspan='2'>[[5ih1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IH1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IH1 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6BQ:PHOSPHORYLATED+JOSAMYCIN'>6BQ</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5igu|5igu]], [[5igv|5igv]], [[5igw|5igw]], [[5igy|5igy]], [[5igz|5igz]], [[5ih0|5ih0]]</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=5ih1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ih1 OCA], [http://pdbe.org/5ih1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ih1 RCSB], [http://www.ebi.ac.uk/pdbsum/5ih1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ih1 ProSAT]</span></td></tr>

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== 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.

 

== References ==

[[Category: Berghuis, A M]]

[[Category: Fong, D H]]

[[Category: Kinase]]

[[Category: Macrolide phosphotransferase]]

[[Category: Transferase]]