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Publication Abstract from PubMed

Glutaminase 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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.