This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


3qyl

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (10:50, 21 February 2024) (edit) (undo)
 
(5 intermediate revisions not shown.)
Line 1: Line 1:
 +
==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='3qyl' size='340' side='right' caption='[[3qyl]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
+
<StructureSection load='3qyl' size='340' side='right'caption='[[3qyl]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[3qyl]] is a 1 chain structure with sequence from [http://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=3QYL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QYL FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[3qyl]] 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=3QYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QYL FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7ME:(7S)-7-METHYL-5,6,7,8-TETRAHYDROQUINAZOLINE-2,4-DIAMINE'>7ME</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></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]] 1.79&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qyo|3qyo]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7ME:(7S)-7-METHYL-5,6,7,8-TETRAHYDROQUINAZOLINE-2,4-DIAMINE'>7ME</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
-
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://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'>[https://proteopedia.org/fgij/fg.htm?mol=3qyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qyl OCA], [https://pdbe.org/3qyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qyl RCSB], [https://www.ebi.ac.uk/pdbsum/3qyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qyl 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=3qyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qyl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qyl RCSB], [http://www.ebi.ac.uk/pdbsum/3qyl PDBsum]</span></td></tr>
+
</table>
</table>
-
<div style="background-color:#fffaf0;">
+
== Function ==
-
== Publication Abstract from PubMed ==
+
[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.
-
Signal 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<ref>PMID:22246400</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
==See Also==
==See Also==
-
*[[Dihydrofolate reductase|Dihydrofolate reductase]]
+
*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
-
== References ==
+
-
<references/>
+
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Dihydrofolate reductase]]
+
[[Category: Escherichia coli K-12]]
-
[[Category: Escherichia coli k-12]]
+
[[Category: Large Structures]]
-
[[Category: Carroll, M J.]]
+
[[Category: Carroll MJ]]
-
[[Category: Collins, E J.]]
+
[[Category: Collins EJ]]
-
[[Category: Gromova, A V.]]
+
[[Category: Gromova AV]]
-
[[Category: Lee, A L.]]
+
[[Category: Lee AL]]
-
[[Category: Mauldin, R V.]]
+
[[Category: Mauldin RV]]
-
[[Category: Singleton, S F.]]
+
[[Category: Singleton SF]]
-
[[Category: Oxidoreductase]]
+
-
[[Category: Reductase]]
+
-
[[Category: Rossmann fold]]
+

Current revision

Sensitivity of receptor internal motions to ligand binding affinity and kinetic off-rate

PDB ID 3qyl

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3qyl"
Personal tools