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==Macrolide 2'-phosphotransferase type I - complex with GDP and oleandomycin==
==Macrolide 2'-phosphotransferase type I - complex with GDP and oleandomycin==
<StructureSection load='5igr' size='340' side='right' caption='[[5igr]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
<StructureSection load='5igr' size='340' side='right'caption='[[5igr]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5igr]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IGR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IGR FirstGlance]. <br>
<table><tr><td colspan='2'>[[5igr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IGR FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene>, <scene name='pdbligand=ZIO:(3S,5R,6S,7R,8R,11R,12S,13R,14S,15S)-6-HYDROXY-5,7,8,11,13,15-HEXAMETHYL-4,10-DIOXO-14-{[3,4,6-TRIDEOXY-3-(DIMETHYLAMINO)-BETA-D-XYLO-HEXOPYRANOSYL]OXY}-1,9-DIOXASPIRO[2.13]HEXADEC-12-YL+2,6-DIDEOXY-3-O-METHYL-ALPHA-L-ARABINO-HEXOPYRANOSIDE'>ZIO</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5igh|5igh]], [[5igi|5igi]], [[5igj|5igj]], [[5igp|5igp]], [[5igs|5igs]], [[5igt|5igt]], [[5igu|5igu]], [[5igv|5igv]], [[5igw|5igw]], [[5igy|5igy]], [[5igz|5igz]], [[5ih0|5ih0]], [[5ih1|5ih1]], [[5iwu|5iwu]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene>, <scene name='pdbligand=ZIO:(3S,5R,6S,7R,8R,11R,12S,13R,14S,15S)-6-HYDROXY-5,7,8,11,13,15-HEXAMETHYL-4,10-DIOXO-14-{[3,4,6-TRIDEOXY-3-(DIMETHYLAMINO)-BETA-D-XYLO-HEXOPYRANOSYL]OXY}-1,9-DIOXASPIRO[2.13]HEXADEC-12-YL+2,6-DIDEOXY-3-O-METHYL-ALPHA-L-ARABINO-HEXOPYRANOSIDE'>ZIO</scene></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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5igr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5igr OCA], [https://pdbe.org/5igr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5igr RCSB], [https://www.ebi.ac.uk/pdbsum/5igr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5igr ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/Q47396_ECOLX Q47396_ECOLX]
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>
==See Also==
 
*[[Phosphotransferase 3D structures|Phosphotransferase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5igr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Berghuis, A M]]
[[Category: Escherichia coli]]
[[Category: Fong, D H]]
[[Category: Large Structures]]
[[Category: Kinase]]
[[Category: Berghuis AM]]
[[Category: Macrolide phosphotransferase]]
[[Category: Fong DH]]
[[Category: Transferase-antibiotic complex]]

Latest revision as of 15:34, 6 March 2024

Macrolide 2'-phosphotransferase type I - complex with GDP and oleandomycinMacrolide 2'-phosphotransferase type I - complex with GDP and oleandomycin

Structural highlights

5igr is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.6Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q47396_ECOLX

See Also

5igr, resolution 1.60Å

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OCA
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