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PDBsum entry 4ou3
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Hydrolase/protein binding
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PDB id
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4ou3
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References listed in PDB file
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Key reference
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Title
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A unified mechanism for aminopeptidase n-Based tumor cell motility and tumor-Homing therapy.
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Authors
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C.Liu,
Y.Yang,
L.Chen,
Y.L.Lin,
F.Li.
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Ref.
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J Biol Chem, 2014,
289,
34520-34529.
[DOI no: ]
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PubMed id
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Abstract
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Tumor cell surface aminopeptidase N (APN or CD13) has two puzzling functions
unrelated to its enzymatic activity: mediating tumor cell motility and serving
as a receptor for tumor-homing peptides (peptides that bring anti-cancer drugs
to tumor cells). To investigate APN-based tumor-homing therapy, we determined
the crystal structure of APN complexed with a tumor-homing peptide containing a
representative Asn-Gly-Arg (NGR) motif. The tumor-homing peptide binds to the
APN enzymatic active site, but it resists APN degradation due to a distorted
scissile peptide bond. To explore APN-based tumor cell motility, we examined the
interactions between APN and extracellular matrix (ECM) proteins. APN binds to,
but does not degrade, NGR motifs in ECM proteins that share similar
conformations with the NGR motif in the APN-bound tumor-homing peptide.
Therefore, APN-based tumor cell motility and tumor-homing therapy rely on a
unified mechanism in which both functions are driven by the specific and stable
interactions between APN and the NGR motifs in ECM proteins and tumor-homing
peptides. This study further implicates APN as an integrin-like molecule that
functions broadly in cell motility and adhesion by interacting with its
signature NGR motifs in the extracellular environment.
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