5IXB: Structure of human Melanoma Inhibitory Activity (MIA) Protein in complex with Pyrimidin-2-amine

Citation:
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.
PDB ID: 5IXBDownload
MMDB ID: 163414
PDB Deposition Date: 2016/3/23
Updated in MMDB: 2018/06
Experimental Method:
x-ray diffraction
Resolution: 1.39  Å
Source Organism:
Similar Structures:
Biological Unit for 5IXB: monomeric; determined by author
Molecular Components in 5IXB
Label Count Molecule
Protein (1 molecule)
1
Melanoma-derived Growth Regulatory Protein(Gene symbol: MIA)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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