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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]] 1.60Å' scene=''> | <StructureSection load='5igr' size='340' side='right'caption='[[5igr]], [[Resolution|resolution]] 1.60Å' 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 [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. 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> | ||
</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='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> | ||
<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='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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mphA, mph(A), mph2, A4X18_25005, A4X18_26080, A6M24_25350, ACM48_26150, AN669_16770, APT94_14590, APZ14_31330, AZ95_0038, ECONIH1_26770, ERS085366_04054, ERS139269_04809, ERS150873_04753, ETN48_p0083, HMPREF3040_01642, orf00017, pCTXM123_C0996_11, pKC394-009, UN86_19875 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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'>[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> | ||
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==See Also== | ==See Also== | ||
*[[Phosphotransferase|Phosphotransferase]] | *[[Phosphotransferase 3D structures|Phosphotransferase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillus coli migula 1895]] | |||
[[Category: Large Structures]] | |||
[[Category: Berghuis, A M]] | [[Category: Berghuis, A M]] | ||
[[Category: Fong, D H]] | [[Category: Fong, D H]] | ||
Revision as of 11:04, 8 January 2020
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. See AlsoReferences
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