4MRE
Crystal structure of the murine CD44 hyaluronan binding domain complex with a small molecule
Summary for 4MRE
| Entry DOI | 10.2210/pdb4mre/pdb |
| Related | 4MRD 4MRF 4MRG 4MRH 4NP2 4NP3 |
| Descriptor | CD44 antigen, DIMETHYL SULFOXIDE, 3-methylbenzene-1,2-diamine, ... (4 entities in total) |
| Functional Keywords | link module, cell receptor, hyaluronan binding, cell surface, cell adhesion-inhibitor complex, cell adhesion/inhibitor |
| Biological source | Mus musculus (mouse) |
| Cellular location | Cell membrane; Single-pass type I membrane protein: P15379 |
| Total number of polymer chains | 1 |
| Total formula weight | 16924.91 |
| Authors | Liu, L.K.,Finzel, B. (deposition date: 2013-09-17, release date: 2014-04-16, Last modification date: 2023-09-20) |
| Primary citation | Liu, L.K.,Finzel, B.C. Fragment-Based Identification of an Inducible Binding Site on Cell Surface Receptor CD44 for the Design of Protein-Carbohydrate Interaction Inhibitors. J.Med.Chem., 57:2714-2725, 2014 Cited by PubMed Abstract: Selective inhibitors of hyaluronan (HA) binding to the cell surface receptor CD44 will have value as probes of CD44-mediated signaling and have potential as therapeutic agents in chronic inflammation, cardiovascular disease, and cancer. Using biophysical binding assays, fragment screening, and crystallographic characterization of complexes with the CD44 HA binding domain, we have discovered an inducible pocket adjacent to the HA binding groove into which small molecules may bind. Iterations of fragment combination and structure-driven design have allowed identification of a series of 1,2,3,4-tetrahydroisoquinolines as the first nonglycosidic inhibitors of the CD44-HA interaction. The affinity of these molecules for the CD44 HA binding domain parallels their ability to interfere with CD44 binding to polymeric HA in vitro. X-ray crystallographic complexes of lead compounds are described and compared to a new complex with a short HA tetrasaccharide, to establish the tetrahydroisoquinoline pharmacophore as an attractive starting point for lead optimization. PubMed: 24606063DOI: 10.1021/jm5000276 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.58 Å) |
Structure validation
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