3qyo: Difference between revisions
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==Sensitivity of receptor internal motions to ligand binding affinity and kinetic off-rate== | ==Sensitivity of receptor internal motions to ligand binding affinity and kinetic off-rate== | ||
<StructureSection load='3qyo' size='340' side='right' caption='[[3qyo]], [[Resolution|resolution]] 2.09Å' scene=''> | <StructureSection load='3qyo' size='340' side='right'caption='[[3qyo]], [[Resolution|resolution]] 2.09Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3qyo]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3qyo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_k-12 Escherichia coli k-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QYO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QYO FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=Q24:QUINAZOLINE-2,4-DIAMINE'>Q24</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=Q24:QUINAZOLINE-2,4-DIAMINE'>Q24</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qyl|3qyl]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qyl|3qyl]]</div></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qyo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qyo OCA], [https://pdbe.org/3qyo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qyo RCSB], [https://www.ebi.ac.uk/pdbsum/3qyo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qyo ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/DYR_ECOLI DYR_ECOLI]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Dihydrofolate reductase|Dihydrofolate reductase]] | *[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Dihydrofolate reductase]] | [[Category: Dihydrofolate reductase]] | ||
[[Category: Escherichia coli k-12]] | [[Category: Escherichia coli k-12]] | ||
[[Category: Large Structures]] | |||
[[Category: Carroll, M J]] | [[Category: Carroll, M J]] | ||
[[Category: Collins, E J]] | [[Category: Collins, E J]] | ||
Revision as of 08:41, 15 June 2022
Sensitivity of receptor internal motions to ligand binding affinity and kinetic off-rateSensitivity of receptor internal motions to ligand binding affinity and kinetic off-rate
Structural highlights
Function[DYR_ECOLI] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Publication Abstract from PubMedSignal transduction, regulatory processes and pharmaceutical responses are highly dependent upon ligand residence times. Gaining insight into how physical factors influence residence times (1/k(off)) should enhance our ability to manipulate biological interactions. We report experiments that yield structural insight into k(off) involving a series of eight 2,4-diaminopyrimidine inhibitors of dihydrofolate reductase whose binding affinities vary by six orders of magnitude. NMR relaxation-dispersion experiments revealed a common set of residues near the binding site that undergo a concerted millisecond-timescale switching event to a previously unidentified conformation. The rate of switching from ground to excited conformations correlates exponentially with the binding affinity K(i) and k(off), suggesting that protein dynamics serves as a mechanical initiator of ligand dissociation within this series and potentially for other macromolecule-ligand systems. Although the forward rate of conformational exchange, k(conf,forward), is faster than k(off), the use of the ligand series allowed for connections to be drawn between kinetic events on different timescales. Evidence for dynamics in proteins as a mechanism for ligand dissociation.,Carroll MJ, Mauldin RV, Gromova AV, Singleton SF, Collins EJ, Lee AL Nat Chem Biol. 2012 Jan 15;8(3):246-52. doi: 10.1038/nchembio.769. PMID:22246400[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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