2L4S

Promiscuous Binding at the Crossroads of Numerous Cancer Pathways: Insight from the Binding of GIP with Glutaminase L

Summary for 2L4S

• Entry DOI: 10.2210/pdb2l4s/pdb
• Related: 2L4T
• NMR Information: BMRB: 17254
• Descriptor: Tax1-binding protein 3 (1 entity in total)
• Functional Keywords: pdz domain, gip, glutatminase l, peptide binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 13751.68

Authors

Zoetewey, D.L.,Ovee, M.,Banerjee, M.,Bhaskaran, R.,Mohanty, S. (deposition date: 2010-10-13, release date: 2011-04-06, Last modification date: 2024-05-15)

Primary citation

Zoetewey, D.L.,Ovee, M.,Banerjee, M.,Bhaskaran, R.,Mohanty, S.
Promiscuous binding at the crossroads of numerous cancer pathways: insight from the binding of glutaminase interacting protein with glutaminase L.
Biochemistry, 50:3528-3539, 2011

PubMed Abstract: The 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 analogue of glutaminase L. This is the first reported nuclear magnetic resonance structure of GIP in a complex with one of its binding partners. Our analysis of both free GIP and GIP in a complex 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.

PubMed: 21417405
DOI: 10.1021/bi102055y

Experimental method

SOLUTION NMR