PDBsum entry 4ou3

Hydrolase/protein binding

PDB id: 4ou3

Contents

Protein chain

902 a.a.

Ligands

CYS-ASN-GLY-ARG-CYS-GLY

NAG-NAG ×8

NAG ×2

SO4 ×10

Metals

_ZN

Waters ×906

PDB id:

4ou3

Name:

Hydrolase/protein binding

Title:

Crystal structure of porcine aminopeptidase n complexed with cngrcg tumor-homing peptide

Structure:

Aminopeptidase n. Chain: a. Fragment: unp residues 63-963. Synonym: ap-n, papn, alanyl aminopeptidase, aminopeptidase m, ap-m, microsomal aminopeptidase, gp130. Engineered: yes. Tumor-homing peptide. Chain: b. Engineered: yes

Source:

Sus scrofa. Pig. Organism_taxid: 9823. Gene: anpep. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Synthetic: yes

Resolution:

1.95Å R-factor: 0.143 R-free: 0.190

Authors:

C.Liu,Y.Yang,L.Chen,Y.-L.Lin,F.Li

Key ref:

C.Liu et al. (2014). A unified mechanism for aminopeptidase N-based tumor cell motility and tumor-homing therapy. J Biol Chem, 289, 34520-34529. PubMed id: 25359769 DOI: 10.1074/jbc.M114.566802

Date:

14-Feb-14 Release date: 05-Nov-14

Protein chain

P15145  (AMPN_PIG) -  Aminopeptidase N from Sus scrofa

Seq: 963 a.a.

Struc: 902 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.4.11.2 - membrane alanyl aminopeptidase.
• Reaction: Release of an N-terminal amino acid, Xaa-|-Xbb- from a peptide, amide or arylamide. Xaa is preferably Ala, but may be most amino acids including Pro (slow action). When a terminal hydrophobic residue is followed by a prolyl residue, the two may be released as an intact Xaa-Pro dipeptide.
• Cofactor: Zn(2+)

DOI no: 10.1074/jbc.M114.566802

J Biol Chem 289:34520-34529 (2014)

PubMed id: 25359769

A unified mechanism for aminopeptidase N-based tumor cell motility and tumor-homing therapy.

C.Liu, Y.Yang, L.Chen, Y.L.Lin, F.Li.

ABSTRACT

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.