6BV0

Crystal structure of porcine aminopeptidase-N with Arginine

6BV0 の概要

• エントリーDOI: 10.2210/pdb6bv0/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900017
• 分子名称: Aminopeptidase N, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: zinc aminopeptidase, hydrolase
• 由来する生物種: Sus scrofa (Pig)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 108765.12

構造登録者

Chen, L.,Lin, Y.-L.,Li, F. (登録日: 2017-12-12, 公開日: 2018-01-17, 最終更新日: 2024-10-30)

主引用文献

Joshi, S.,Chen, L.,Winter, M.B.,Lin, Y.L.,Yang, Y.,Shapovalova, M.,Smith, P.M.,Liu, C.,Li, F.,LeBeau, A.M.
The Rational Design of Therapeutic Peptides for Aminopeptidase N using a Substrate-Based Approach.
Sci Rep, 7:1424-, 2017

PubMed Abstract: The M1 family of metalloproteases represents a large number of exopeptidases that cleave single amino acid residues from the N-terminus of peptide substrates. One member of this family that has been well studied is aminopeptidase N (APN), a multifunctional protease known to cleave biologically active peptides and aide in coronavirus entry. The proteolytic activity of APN promotes cancer angiogenesis and metastasis making it an important target for cancer therapy. To understand the substrate specificity of APN for the development of targeted inhibitors, we used a global substrate profiling method to determine the P1-P4' amino acid preferences. The key structural features of the APN pharmacophore required for substrate recognition were elucidated by x-ray crystallography. By combining these substrate profiling and structural data, we were able to design a selective peptide inhibitor of APN that was an effective therapeutic both in vitro and in vivo against APN-expressing prostate cancer models.

PubMed: 28465619
DOI: 10.1038/s41598-017-01542-5

実験手法

X-RAY DIFFRACTION (1.86 Å)