5OLF

Ligand-Based NMR Study of C-X-C Chemokine Receptor Type 4 (CXCR4)-Ligand Interactions in Living Cancer Cells

Summary for 5OLF

• Entry DOI: 10.2210/pdb5olf/pdb
• NMR Information: BMRB: 34166
• Descriptor: GBA-ALA-CYS-ARG-PHE-PHE-CYS (1 entity in total)
• Functional Keywords: cxcr4, peptide binding protein, in-cell nmr
• Biological source: Homo sapiens
• Total number of polymer chains: 1
• Total formula weight: 909.09

Authors

Brancaccio, D.,Carotenuto, A. (deposition date: 2017-07-27, release date: 2018-06-06, Last modification date: 2024-10-23)

Primary citation

Brancaccio, D.,Diana, D.,Di Maro, S.,Di Leva, F.S.,Tomassi, S.,Fattorusso, R.,Russo, L.,Scala, S.,Trotta, A.M.,Portella, L.,Novellino, E.,Marinelli, L.,Carotenuto, A.
Ligand-Based NMR Study of C-X-C Chemokine Receptor Type 4 (CXCR4)-Ligand Interactions on Living Cancer Cells.
J. Med. Chem., 61:2910-2923, 2018

PubMed Abstract: Peptide-binding G protein-coupled receptors (GPCRs) are key effectors in numerous pathological and physiological pathways. The assessment of the receptor-bound conformation of a peptidic ligand within a membrane receptor such as a GPCR is of great impact for a rational drug design of more potent analogues. In this work, we applied multiple ligand-based nuclear magnetic resonance (NMR) methods to study the interaction of peptide heptamers, derived from the C-X-C Motif Chemokine 12 (CXCL12), and the C-X-C Chemokine Receptor Type 4 (CXCR4) on membranes of human T-Leukemia cells (CCRF-CEM cells). This study represents the first structural investigation reporting the receptor-bound conformation of a peptide to a GPCR directly on a living cell. The results obtained in the field of CXCL12/CXCR4 are proofs of concept, although important information for researchers dealing with the CXCR4 field arises. General application of the presented NMR methodologies is possible and surely may help to boost the development of new therapeutic agents targeting GPCRs.

PubMed: 29522685
DOI: 10.1021/acs.jmedchem.7b01830

Experimental method

SOLUTION NMR