View source for 4nxp


==Crystal Structure of Free T-cell Lymphoma Invasion and Metastasis-1 PDZ Domain Quadruple Mutant (QM)==
<StructureSection load='4nxp' size='340' side='right'caption='[[4nxp]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4nxp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NXP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NXP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</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=4nxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nxp OCA], [https://pdbe.org/4nxp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nxp RCSB], [https://www.ebi.ac.uk/pdbsum/4nxp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nxp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TIAM1_HUMAN TIAM1_HUMAN] Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Activates RAC1, CDC42, and to a lesser extent RHOA.
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== Publication Abstract from PubMed ==
Conformational dynamics has an established role in enzyme catalysis, but its contribution to ligand binding and specificity is largely unexplored. Here we used the Tiam1 PDZ domain and an engineered variant (QM PDZ) with broadened specificity to investigate the role of structure and conformational dynamics in molecular recognition. Crystal structures of the QM PDZ domain both free and bound to ligands showed structural features central to binding (enthalpy), while nuclear-magnetic-resonance-based methyl relaxation experiments and isothermal titration calorimetry revealed that conformational entropy contributes to affinity. In addition to motions relevant to thermodynamics, slower microsecond to millisecond switching was prevalent in the QM PDZ ligand-binding site consistent with a role in ligand specificity. Our data indicate that conformational dynamics plays distinct and fundamental roles in tuning the affinity (conformational entropy) and specificity (excited-state conformations) of molecular interactions. More broadly, our results have important implications for the evolution, regulation, and design of protein-ligand interactions.

Distinct Roles for Conformational Dynamics in Protein-Ligand Interactions.,Liu X, Speckhard DC, Shepherd TR, Sun YJ, Hengel SR, Yu L, Fowler CA, Gakhar L, Fuentes EJ Structure. 2016 Dec 6;24(12):2053-2066. doi: 10.1016/j.str.2016.08.019. Epub 2016, Oct 27. PMID:27998539<ref>PMID:27998539</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fuentes EJ]]
[[Category: Hengel SR]]
[[Category: Liu X]]
[[Category: Shepherd TR]]
[[Category: Speckhard DC]]