9QA0

Drosophila melanogaster angiotensin converting enzyme homologue, AnCE in complex with IW dipeptide

9QA0 の概要

• エントリーDOI: 10.2210/pdb9qa0/pdb
• 分子名称: Angiotensin-converting enzyme, ILE-TRP dipeptide, beta-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]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, dipeptides, hypertension, hydrolase
• 由来する生物種: Drosophila melanogaster (fruit fly); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 71569.31

構造登録者

Zukowska, J.,Gregory, K.S.,Acharya, K.R. (登録日: 2025-02-27, 公開日: 2025-05-14)

主引用文献

Zukowska, J.,Gregory, K.S.,Robinson, A.,Isaac, R.E.,Acharya, K.R.
Molecular Basis of Dipeptide Recognition in Drosophila melanogaster Angiotensin I-Converting Enzyme Homologue, AnCE.
Biomolecules, 15:-, 2025

PubMed Abstract: Human angiotensin-I-converting enzyme (ACE) is involved in vasoregulation, inflammation, and neurodegenerative disorders. The enzyme is formed of two domains; the C-domain (cACE) is primarily involved in blood pressure regulation, whereas the N-domain (nACE) is strongly linked to fibrosis; hence, designing domain-specific inhibitors could make a difference between treating one condition without having a negative effect on another. AnCE (a close homologue of ACE) is derived from and has a high similarity specifically to cACE. Due to high similarity and ease of crystallisation, AnCE has been chosen as a model protein for ACE studies and for the design of ACE inhibitors. In this study, enzyme kinetic assays and X-ray crystallography techniques revealed the significance of using dipeptides as selective inhibitors for AnCE and how this knowledge could be applied to cACE and nACE. All the dipeptides tested in this study were shown to bind AnCE in two distinct locations, i.e., the non-prime and prime subsites. It was found that a hydrophobic residue at the S1 and S1' subsites, with a tryptophan at the S2 and S2' subsites, showed highest affinity towards AnCE. It was also observed that a key pocket within the S2' subsite had a major influence on the binding orientation within the prime subsites and could potentially explain ACE's dipeptidyl carboxypeptidase activity. Importantly these dipeptides are found in functional foods, making them potentially available from diets. Knowledge of the dipeptide binding presented here could aid in the development of ACE domain-specific inhibitors.

PubMed: 40305366
DOI: 10.3390/biom15040591

実験手法

X-RAY DIFFRACTION (2.2 Å)