4UFA

Crystal structure of the Angiotensin-1 converting enzyme N-domain in complex with Ac-SD

4UFA の概要

• エントリーDOI: 10.2210/pdb4ufa/pdb
• 関連するPDBエントリー: 4UFB 5AM8 5AM9 5AMA 5AMB 5AMC
• 分子名称: ANGIOTENSIN-CONVERTING ENZYME, HEXAETHYLENE GLYCOL, N-ACETYL-SERINE, ... (13 entities in total)
• 機能のキーワード: hydrolase, angiotensin-converting enzyme, metalloprotease, n-acetyl-ser-asp-lys-pro
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 149800.07

構造登録者

Masuyer, G.,Douglas, R.G.,Sturrock, E.D.,Acharya, K.R. (登録日: 2015-03-16, 公開日: 2015-10-07, 最終更新日: 2024-11-13)

主引用文献

Masuyer, G.,Douglas, R.G.,Sturrock, E.D.,Acharya, K.R.
Structural Basis of Ac-Sdkp Hydrolysis by Angiotensin-I Converting Enzyme
Sci.Rep., 5:13742-, 2015

PubMed Abstract: Angiotensin-I converting enzyme (ACE) is a zinc dipeptidylcarboxypeptidase with two active domains and plays a key role in the regulation of blood pressure and electrolyte homeostasis, making it the principal target in the treatment of cardiovascular disease. More recently, the tetrapetide N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP) has emerged as a potent antifibrotic agent and negative regulator of haematopoietic stem cell differentiation which is processed exclusively by ACE. Here we provide a detailed biochemical and structural basis for the domain preference of Ac-SDKP. The high resolution crystal structures of N-domain ACE in complex with the dipeptide products of Ac-SDKP cleavage were obtained and offered a template to model the mechanism of substrate recognition of the enzyme. A comprehensive kinetic study of Ac-SDKP and domain co-operation was performed and indicated domain interactions affecting processing of the tetrapeptide substrate. Our results further illustrate the molecular basis for N-domain selectivity and should help design novel ACE inhibitors and Ac-SDKP analogues that could be used in the treatment of fibrosis disorders.

PubMed: 26403559
DOI: 10.1038/SREP13742

実験手法

X-RAY DIFFRACTION (1.8 Å)