4FYS

Human aminopeptidase N (CD13) in complex with angiotensin IV

4FYS の概要

• エントリーDOI: 10.2210/pdb4fys/pdb
• 関連するPDBエントリー: 4FYQ 4FYR 4FYT
• 分子名称: Aminopeptidase N, Angiotensin IV, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: metalloprotease, hydrolase-hormone complex, hydrolase/hormone
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 107200.32

構造登録者

Wong, A.H.,Rini, J.M. (登録日: 2012-07-05, 公開日: 2012-09-05, 最終更新日: 2024-10-30)

主引用文献

Wong, A.H.,Zhou, D.,Rini, J.M.
The X-ray Crystal Structure of Human Aminopeptidase N Reveals a Novel Dimer and the Basis for Peptide Processing.
J.Biol.Chem., 287:36804-36813, 2012

PubMed Abstract: Human aminopeptidase N (hAPN/hCD13) is a dimeric membrane protein and a member of the M1 family of zinc metallopeptidases. Within the rennin-angiotensin system, its enzymatic activity is responsible for processing peptide hormones angiotensin III and IV. In addition, hAPN is also involved in cell adhesion, endocytosis, and signal transduction and it is an important target for cancer therapy. Reported here are the high resolution x-ray crystal structures of the dimeric ectodomain of hAPN and its complexes with angiotensin IV and the peptidomimetic inhibitors, amastatin and bestatin. Each monomer of the dimer is found in what has been termed the closed form in other M1 enzymes and each monomer is characterized by an internal cavity surrounding the catalytic site as well as a unique substrate/inhibitor-dependent loop ordering, which in the case of the bestatin complex suggests a new route to inhibitor design. The hAPN structure provides the first example of a dimeric M1 family member and the observed structural features, in conjunction with a model for the open form, provide novel insights into the mechanism of peptide processing and signal transduction.

PubMed: 22932899
DOI: 10.1074/jbc.M112.398842

実験手法

X-RAY DIFFRACTION (2.01 Å)