文献类型：期刊文献

英文题名：Inhibitory mechanism of a substrate-type angiotensin I-converting enzyme inhibitory peptide

作者：Wu, Junjie[1];Xie, Dewei[1];Chen, Xujun[1];Tang, Ya-Jie[2];Wang, Lixin[3];Xie, Jingli[1,4];Wei, Dongzhi[1,4]

机构：[1]East China Univ Sci & Technol, Sch Biotechnol, Dept Food Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Hubei Univ Technol, Hubei Prov Cooperat Innovat Ctr Ind Fermentat, Hubei Key Lab Ind Microbiol, Key Lab Fermentat Engn,Minist Educ, Wuhan 430068, Hubei, Peoples R China;[3]Tongji Univ, Sports Hlth Ctr, Shanghai 200092, Peoples R China;[4]SCICB, Shanghai 200237, Peoples R China

年份：2019

卷号：79

起止页码：97

外文期刊名：PROCESS BIOCHEMISTRY

收录：;EI(收录号：20190206350232);WOS:【SCI-EXPANDED(收录号:WOS:000466621000013)】；

基金：This work was supported by the Open Funding Project of Key Laboratory of Fermentation Engineering (Ministry of Education) of China, and the Opening Project of Shanghai Key Laboratory of New Drug Design (Grant No. 17DZ2271000), China.

语种：英文

外文关键词：Substrate-type ACE inhibitory peptide; Inhibitory mechanism; ITC; Molecular docking

摘要：The inhibitory mechanism during the reaction between peptides from Phascolosoma esculenta and angiotensin I converting enzyme (ACE) was studied. Thermodynamics features of the peptide-ACE binding reaction measured by isothermal titration calorimetry (ITC) assay, combining with the decrease of ACE inhibition within 24 h implied that Gly-Asn-Gly-Ser-Gly-Tyr-Val-Ser-Arg decomposed during the reaction and played as a substrate type inhibitor. The hydrolysate Gly-Asn-Gly-Ser-Gly-Tyr-Val (GNGSGYV) without ACE inhibitory activity was identified by UPLC & Q-TOF MS, while the hydrolysate Ser-Arg (SR) showed competitive inhibition of ACE with IC50 value of 790 mu M. However, GNGSGYV and SR have synergistic effect on ACE and result in an ACE inhibitory IC50 value of 170 mu M. The synergistic mechanism illustrated by two-step molecular docking discovered that SR firstly attacked the catalytic Zn of ACE and formed coordinate bond, and then GNGSGYV bound with the arginine of SR and residues along the channel of ACE active site by hydrogen bonds to block the substrate from entering. The circular dichroism spectra also verified that SR and GNGSGYV significantly changed the secondary structure of ACE.