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PDBsum entry 5ixb
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Cell adhesion
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PDB id
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5ixb
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PDB id:
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| Name: |
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Cell adhesion
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Title:
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Structure of human melanoma inhibitory activity (mia) protein in complex with pyrimidin-2-amine
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Structure:
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Melanoma-derived growth regulatory protein. Chain: a, b. Fragment: unp residues 25-131. Synonym: melanoma inhibitory activity protein. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: mia. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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1.39Å
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R-factor:
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0.134
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R-free:
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0.160
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Authors:
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K.T.Yip,R.Gasper,X.Y.Zhong,N.Seibel,S.Puetz,J.Autzen,J.Scherkenbeck, E.Hofmann,R.Stoll
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Key ref:
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K.T.Yip
et al.
(2016).
Small Molecules Antagonise the MIA-Fibronectin Interaction in Malignant Melanoma.
Sci Rep,
6,
25119.
PubMed id:
DOI:
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Date:
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23-Mar-16
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Release date:
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17-Aug-16
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PROCHECK
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Headers
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References
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Q16674
(MIA_HUMAN) -
Melanoma-derived growth regulatory protein from Homo sapiens
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Seq:
Struc:
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131 a.a.
105 a.a.
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Key: |
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Secondary structure |
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CATH domain |
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DOI no:
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Sci Rep
6:25119
(2016)
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PubMed id:
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Small Molecules Antagonise the MIA-Fibronectin Interaction in Malignant Melanoma.
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K.T.Yip,
X.Y.Zhong,
N.Seibel,
S.Pütz,
J.Autzen,
R.Gasper,
E.Hofmann,
J.Scherkenbeck,
R.Stoll.
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ABSTRACT
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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.
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Links
