7f0b: Difference between revisions
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==Crystal structure of capreomycin phosphotransferase in complex with ATP== | ==Crystal structure of capreomycin phosphotransferase in complex with ATP== | ||
<StructureSection load='7f0b' size='340' side='right'caption='[[7f0b]]' scene=''> | <StructureSection load='7f0b' size='340' side='right'caption='[[7f0b]], [[Resolution|resolution]] 2.14Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7F0B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F0B FirstGlance]. <br> | <table><tr><td colspan='2'>[[7f0b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharothrix_mutabilis_subsp._capreolus Saccharothrix mutabilis subsp. capreolus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7F0B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F0B FirstGlance]. <br> | ||
</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=7f0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f0b OCA], [https://pdbe.org/7f0b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f0b RCSB], [https://www.ebi.ac.uk/pdbsum/7f0b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f0b ProSAT]</span></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]] 2.14Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></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=7f0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f0b OCA], [https://pdbe.org/7f0b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f0b RCSB], [https://www.ebi.ac.uk/pdbsum/7f0b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f0b ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q53826_STRMP Q53826_STRMP] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Capreomycin (CMN) is an important second-line antituberculosis antibiotic isolated from Saccharothrix mutabilis subspecies capreolus. The gene cluster for CMN biosynthesis has been identified and sequenced, wherein the cph gene was annotated as a phosphotransferase likely engaging in self-resistance. Previous studies reported that Cph inactivates two CMNs, CMN IA and IIA, by phosphorylation. We, herein, report that (1) Escherichia coli harboring the cph gene becomes resistant to both CMN IIA and IIB, (2) phylogenetic analysis regroups Cph to a new clade in the phosphotransferase protein family, (3) Cph shares a three-dimensional structure akin to the aminoglycoside phosphotransferases with a high binding affinity (KD) to both CMN IIA and IIB at micromolar levels, and (4) Cph utilizes either ATP or GTP as a phosphate group donor transferring its gamma-phosphate to the hydroxyl group of CMN IIA. Until now, Cph and Vph (viomycin phosphotransferase) are the only two known enzymes inactivating peptide-based antibiotics through phosphorylation. Our biochemical characterization and structural determination conclude that Cph confers the gene-carrying species resistance to CMN by means of either chemical modification or physical sequestration, a naturally manifested belt and braces strategy. These findings add a new chapter into the self-resistance of bioactive natural products, which is often overlooked while designing new bioactive molecules. | |||
Dual-Mechanism Confers Self-Resistance to the Antituberculosis Antibiotic Capreomycin.,Pan YC, Wang YL, Toh SI, Hsu NS, Lin KH, Xu Z, Huang SC, Wu TK, Li TL, Chang CY ACS Chem Biol. 2022 Jan 21;17(1):138-146. doi: 10.1021/acschembio.1c00799. Epub, 2022 Jan 7. PMID:34994196<ref>PMID:34994196</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7f0b" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Phosphotransferase 3D structures|Phosphotransferase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Saccharothrix mutabilis subsp. capreolus]] | |||
[[Category: Chang CY]] | [[Category: Chang CY]] | ||
[[Category: Pan YC]] | [[Category: Pan YC]] | ||
[[Category: Toh SI]] | [[Category: Toh SI]] | ||
[[Category: Wang YL]] | [[Category: Wang YL]] | ||