摘要
利用分子柔性对接方法模拟研究4种较典型的血管紧张素转化酶Ⅰ(ACE)抑制肽KVLPVP(Lys-Val-Leu-Pro-Val-Pro)、YKVPQL(Tyr-Lys-Val-Pro-Gln-Leu)、VYPFPG(Val-Tyr-Pro-Phe-Pro-Gly)、IASGQP(Ile-Ala-Ser-Gly-Gln-Pro)与ACE相互作用的分子机理,确定它们的作用位点、作用力类型及相互作用能。结果表明:4种ACE抑制肽与ACE的活性口袋之间存在氢键、疏水、亲水、静电力、配位键等相互作用力,它们共同维持了肽与ACE复合物构象的稳定。ACE活性口袋中的关键氨基酸残基为:His353、Ala354、Ser355、Ala356、Glu384、Glu411、Pro519、Arg522、Tyr523,小肽分子中的关键基团为:氮端氨基、肽键羰基、碳端羧基;KVLPVP、YKVPQL、VYPFPG、IASGQP与ACE之间的结合能呈由低到高的趋势,表明它们与ACE之间的结合依次减弱,这与它们的IC50值依次增大的趋势相一致。
An investigation into the molecular mechanisms of interaction between angiotensinⅠ-converting enzyme（ACE） and each of four typical ACE-inhibitory peptides derived from milk proteins,KVLPVP（Lys-Val-Leu-Pro-Val-Pro）,YKVPQL（Tyr-Lys-Val-Pro-Gln-Leu）,VYPFPG（Val-Tyr-Pro-Phe-Pro-Gly）,and IASGQP（Ile-Ala-Ser-Gly-Gln-Pro） was carried out using the flexible molecule docking technology to determine the action sites,types of intermolecular force and interaction energy between them.It was shown that hydrogen bond,hydrophobic,hydrophilic and electrostatic interactions and coordinate bond（Zn2＋） existed between the active pockets of ACE and each of the studied ACE-inhibitory peptides,which were together responsible for maintaining the conformational stability of the complexes.The key amino acid residues in the active pockets were His 353,Ala 354,Ser 355,Ala 356,Glu 384,Glu 411,Pro 519,Arg 522 and Tyr 523 and the key groups in the small peptides N-terminal amino groups,carbonyl groups of peptide bonds,C-terminal carboxyl groups.The ACE-inhibitory peptides could be ranked in increasing order of interaction energy between ACE and each of them as follows： KVLPVP,YKVPQL,VYPFPG,and IASGQP.As a consequence,their binding with ACE decreased and the IC50 values increased in the same order.
出处
《食品科学》
EI
CAS
CSCD
北大核心
2011年第23期21-27,共7页
Food Science
基金
江苏省自然科学基金项目(BK2009403)
江苏省科技支撑计划项目(BE2009366)
关键词
ACE抑制肽
血管紧张素转化酶
分子模拟
ACE-inhibitory peptides
angiotensin Ⅰ-converting enzyme
molecular modeling
