2l4s | pdb_00002l4s
Promiscuous Binding at the Crossroads of Numerous Cancer Pathways: Insight from the Binding of GIP with Glutaminase L
Structural highlights
FunctionTX1B3_HUMAN May regulate a number of protein-protein interactions by competing for PDZ domain binding sites. Binds CTNNB1 and may thereby act as an inhibitor of the Wnt signaling pathway. Competes with LIN7A for KCNJ4 binding, and thereby promotes KCNJ4 internalization. May play a role in the Rho signaling pathway. May play a role in activation of CDC42 by the viral protein HPV16 E6.[1] [2] [3] Publication Abstract from PubMedGlutaminase Interacting Protein (GIP) is composed of a single PDZ domain that interacts with a growing list of partner proteins, including Glutaminase L, that are involved in a number of cell signaling and cancer pathways. Therefore, GIP makes a good target for structure-based drug design. Here we report the solution structures of both free GIP and GIP bound to the C-terminal peptide analog of Glutaminase L. This is the first reported NMR structure of GIP in a complex with one of its binding partners. Our analysis of both free GIP and GIP complexed with the Glutaminase L peptide provides important insights into how a promiscuous binding domain can have affinity for multiple binding partners. Through a detailed chemical shift perturbation analysis and backbone dynamics studies, we demonstrate here that the binding of the Glutaminase L peptide to GIP is an allosteric event. Taken together, the insights reported here lay the groundwork for the future development of a specific inhibitor for GIP. Promiscuous Binding at the Crossroads of Numerous Cancer Pathways: Insight from the Binding of GIP with Glutaminase L.,Zoetewey DL, Ovee M, Banerjee M, Bhaskaran R, Mohanty S Biochemistry. 2011 Mar 18. PMID:21417405[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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