5IXB

Structure of human Melanoma Inhibitory Activity (MIA) Protein in complex with Pyrimidin-2-amine

Summary for 5IXB

• Entry DOI: 10.2210/pdb5ixb/pdb
• Descriptor: Melanoma-derived growth regulatory protein, PYRIMIDIN-2-AMINE, ACETATE ION, ... (4 entities in total)
• Functional Keywords: all beta, sh3 domain-like fold, extracellular, cell adhesion
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted: Q16674
• Total number of polymer chains: 2
• Total formula weight: 24824.57

Authors

Yip, K.T.,Gasper, R.,Zhong, X.Y.,Seibel, N.,Puetz, S.,Autzen, J.,Scherkenbeck, J.,Hofmann, E.,Stoll, R. (deposition date: 2016-03-23, release date: 2016-08-17, Last modification date: 2024-11-13)

Primary citation

Yip, K.T.,Zhong, X.Y.,Seibel, N.,Putz, S.,Autzen, J.,Gasper, R.,Hofmann, E.,Scherkenbeck, J.,Stoll, R.
Small Molecules Antagonise the MIA-Fibronectin Interaction in Malignant Melanoma.
Sci Rep, 6:25119-25119, 2016

PubMed Abstract: Melanoma inhibitory activity (MIA), an extracellular protein highly expressed by malignant melanoma cells, plays an important functional role in melanoma development, progression, and metastasis. After its secretion, MIA directly interacts with extracellular matrix proteins, such as fibronectin (FN). By this mechanism, MIA actively facilitates focal cell detachment from surrounding structures and strongly promotes tumour cell invasion and migration. Hence, the molecular understanding of MIA's function provides a promising target for the development of new strategies in malignant melanoma therapy. Here, we describe for the first time the discovery of small molecules that are able to disrupt the MIA-FN complex by selectively binding to a new druggable pocket, which we could identify on MIA by structural analysis and fragment-based screening. Our findings may inspire novel drug discovery efforts aiming at a therapeutically effective treatment of melanoma by targeting MIA.

PubMed: 27151361
DOI: 10.1038/srep25119

Experimental method

X-RAY DIFFRACTION (1.39 Å)