Structural highlights
4nxq is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Related: | 3kzd, 3kze, 4gvd, 4gvc, 4nxr, 4nxp |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[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. [CNTP4_HUMAN] Presynaptic protein involved in both dopaminergic synaptic transmission and GABAergic system, thereby participating in the structural maturation of inhibitory interneuron synapses. Involved in the dopaminergic synaptic transmission by attenuating dopamine release through a presynaptic mechanism. Also participates in the GABAergic system (By similarity).
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liu X, Speckhard DC, Shepherd TR, Sun YJ, Hengel SR, Yu L, Fowler CA, Gakhar L, Fuentes EJ. Distinct Roles for Conformational Dynamics in Protein-Ligand Interactions. Structure. 2016 Dec 6;24(12):2053-2066. doi: 10.1016/j.str.2016.08.019. Epub 2016, Oct 27. PMID:27998539 doi:http://dx.doi.org/10.1016/j.str.2016.08.019
