6yvx: Difference between revisions
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==HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with bicyclic BB-287== | ==HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with bicyclic BB-287== | ||
<StructureSection load='6yvx' size='340' side='right'caption='[[6yvx]]' scene=''> | <StructureSection load='6yvx' size='340' side='right'caption='[[6yvx]], [[Resolution|resolution]] 1.80Å' 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=6YVX OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YVX FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2JP:4-(isoquinolin-3-ylamino)-4-oxobutanoic+acid'>2JP</scene>, <scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=6yvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yvx OCA], [https://pdbe.org/6yvx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yvx RCSB], [https://www.ebi.ac.uk/pdbsum/6yvx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yvx ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Crystallization is the bottleneck in macromolecular crystallography; even when a protein crystallises, crystal packing often influences ligand-binding and protein-protein interaction interfaces, which are the key points of interest for functional and drug discovery studies. The human hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) readily crystallises as a homotrimer, but with a sterically blocked active site. We explored strategies aimed at altering PHD2 crystal packing by protein modification and molecules that bind at its active site and elsewhere. Following the observation that, despite weak inhibition/binding in solution, succinamic acid derivatives readily enable PHD2 crystallization, we explored methods to induce crystallization without active site binding. Cyclic peptides obtained via mRNA display bind PHD2 tightly away from the active site. They efficiently enable PHD2 crystallization in different forms, both with/without substrates, apparently by promoting oligomerization involving binding to the C-terminal region. Although our work involves a specific case study, together with those of others, the results suggest that mRNA display-derived cyclic peptides may be useful in challenging protein crystallization cases. | |||
Use of cyclic peptides to induce crystallization: case study with prolyl hydroxylase domain 2.,Chowdhury R, Abboud MI, McAllister TE, Banerji B, Bhushan B, Sorensen JL, Kawamura A, Schofield CJ Sci Rep. 2020 Dec 15;10(1):21964. doi: 10.1038/s41598-020-76307-8. PMID:33319810<ref>PMID:33319810</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6yvx" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Polyl hydroxylase domain 3D structures|Polyl hydroxylase domain 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 16:20, 6 November 2024
HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with bicyclic BB-287HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with bicyclic BB-287
Structural highlights
Publication Abstract from PubMedCrystallization is the bottleneck in macromolecular crystallography; even when a protein crystallises, crystal packing often influences ligand-binding and protein-protein interaction interfaces, which are the key points of interest for functional and drug discovery studies. The human hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) readily crystallises as a homotrimer, but with a sterically blocked active site. We explored strategies aimed at altering PHD2 crystal packing by protein modification and molecules that bind at its active site and elsewhere. Following the observation that, despite weak inhibition/binding in solution, succinamic acid derivatives readily enable PHD2 crystallization, we explored methods to induce crystallization without active site binding. Cyclic peptides obtained via mRNA display bind PHD2 tightly away from the active site. They efficiently enable PHD2 crystallization in different forms, both with/without substrates, apparently by promoting oligomerization involving binding to the C-terminal region. Although our work involves a specific case study, together with those of others, the results suggest that mRNA display-derived cyclic peptides may be useful in challenging protein crystallization cases. Use of cyclic peptides to induce crystallization: case study with prolyl hydroxylase domain 2.,Chowdhury R, Abboud MI, McAllister TE, Banerji B, Bhushan B, Sorensen JL, Kawamura A, Schofield CJ Sci Rep. 2020 Dec 15;10(1):21964. doi: 10.1038/s41598-020-76307-8. PMID:33319810[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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