6im8: Difference between revisions
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<StructureSection load='6im8' size='340' side='right'caption='[[6im8]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='6im8' size='340' side='right'caption='[[6im8]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6im8]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IM8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IM8 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6im8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IM8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IM8 FirstGlance]. <br> | ||
</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=6im8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6im8 OCA], [http://pdbe.org/6im8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6im8 RCSB], [http://www.ebi.ac.uk/pdbsum/6im8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6im8 ProSAT]</span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cueO, yacK, b0123, JW0119 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=6im8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6im8 OCA], [http://pdbe.org/6im8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6im8 RCSB], [http://www.ebi.ac.uk/pdbsum/6im8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6im8 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Protein-protein interactions (PPIs) are ubiquitous in almost all biological processes and are often corrupted in diseased states. A detailed understanding of PPIs is therefore key to understanding cellular physiology and can yield attractive therapeutic targets. Here, we describe the development and structural characterization of novel Escherichia coli CueO multi-copper oxidase variants engineered to recapitulate protein-protein interactions with commensurate modulation of their enzymatic activities. The fully integrated single-protein sensors were developed through modular grafting of ligand-specific peptides into a highly compliant and flexible methionine-rich loop of CueO. Sensitive detection of diverse ligand classes exemplified by antibodies, an E3 ligase, MDM2 proto-oncogene (MDM2), and protease (SplB from Staphylococcus aureus) was achieved in a simple mix and measure homogeneous format with visually observable colorimetric readouts. Therapeutic antagonism of MDM2 by small molecules and peptides in clinical development for treatment of cancer patients was assayed using the MDM2-binding CueO enzyme. Structural characterization of the free and MDM2-bound CueO variant provided functional insight into signal-transducing mechanisms of the engineered enzymes and highlighted the robustness of CueO as a stable and compliant scaffold for multiple applications. | |||
Development and structural characterization of an engineered multi-copper oxidase reporter of protein-protein interactions.,Sana B, Chee SMQ, Wongsantichon J, Raghavan S, Robinson RC, Ghadessy FJ J Biol Chem. 2019 Apr 26;294(17):7002-7012. doi: 10.1074/jbc.RA118.007141. Epub, 2019 Feb 15. PMID:30770473<ref>PMID:30770473</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6im8" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Blue copper oxidase CueO 3D structures|Blue copper oxidase CueO 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Ecoli]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Ghadessy, F]] | [[Category: Ghadessy, F]] | ||
Revision as of 09:16, 7 August 2019
CueO-PM2 multicopper oxidaseCueO-PM2 multicopper oxidase
Structural highlights
Publication Abstract from PubMedProtein-protein interactions (PPIs) are ubiquitous in almost all biological processes and are often corrupted in diseased states. A detailed understanding of PPIs is therefore key to understanding cellular physiology and can yield attractive therapeutic targets. Here, we describe the development and structural characterization of novel Escherichia coli CueO multi-copper oxidase variants engineered to recapitulate protein-protein interactions with commensurate modulation of their enzymatic activities. The fully integrated single-protein sensors were developed through modular grafting of ligand-specific peptides into a highly compliant and flexible methionine-rich loop of CueO. Sensitive detection of diverse ligand classes exemplified by antibodies, an E3 ligase, MDM2 proto-oncogene (MDM2), and protease (SplB from Staphylococcus aureus) was achieved in a simple mix and measure homogeneous format with visually observable colorimetric readouts. Therapeutic antagonism of MDM2 by small molecules and peptides in clinical development for treatment of cancer patients was assayed using the MDM2-binding CueO enzyme. Structural characterization of the free and MDM2-bound CueO variant provided functional insight into signal-transducing mechanisms of the engineered enzymes and highlighted the robustness of CueO as a stable and compliant scaffold for multiple applications. Development and structural characterization of an engineered multi-copper oxidase reporter of protein-protein interactions.,Sana B, Chee SMQ, Wongsantichon J, Raghavan S, Robinson RC, Ghadessy FJ J Biol Chem. 2019 Apr 26;294(17):7002-7012. doi: 10.1074/jbc.RA118.007141. Epub, 2019 Feb 15. PMID:30770473[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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