Role of a propeller loop in the quaternary structure and enzymatic activity of prolyl dipeptidases DPP-IV and DPP9
Role of a propeller loop in the quaternary structure and enzymatic activity of prolyl dipeptidases DPP-IV and DPP9
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DOI：
10.1016/j.febslet.2011.10.009
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发表时间：
2011-11-04
期刊：
影响因子：
3.5
通讯作者：
Chen, Xin
中科院分区：
文献类型：
--
作者：
Tang, Hung-Kuan;Chen, Ku-Chuan;Chen, Xin
二肽基肽酶(DPP)家族成员包括DPP-IV、DPP8、DPP9等，在倒数第二个脯氨酸残基后裂解肽键，富含药物靶标。DPP-IV的活性需要二聚化。位于二聚体界面的螺旋桨环在该家族中高度保守。在这里，我们对DPPIV的环路进行了定点突变，并确定了几个对二聚体形成和酶活性重要的残基。有趣的是，DPP9上相应的残基有不同的影响，因此突变降低了活性，而不改变二聚化。因此，螺旋桨环在不同的DPP中似乎扮演着不同的角色。蛋白质相互作用结构概述：DPP-IV和DPP-IV在凝胶电泳中通过共迁移相互作用(View相互作用：1，2，3，4)DPP9和DPP9通过圆二向色性结合(View相互作用)DPP-IV和DPP-IV通过圆二色谱结合(View相互作用：1，2，3，4，5)DPP-IV和DPP-IV在溶液中通过共构建结合(View相互作用：1，2，3，4，5)ADA通过表面等离子共振结合DPP-IV(View相互作用：1，2，3，4，56)DPP9和DPP9在溶液中通过共沉淀结合(查看交互作用)(C)2011年欧洲生化学会联合会。爱思唯尔出版公司版权所有。
The dipeptidyl peptidase (DPP) family members, including DPP-IV, DPP8, DPP9 and others, cleave the peptide bond after the penultimate proline residue and are drug target rich. The dimerization of DPP-IV is required for its activity. A propeller loop located at the dimer interface is highly conserved within the family. Here we carried out site-directed mutagenesis on the loop of DPPIV and identified several residues important for dimer formation and enzymatic activity. Interestingly, the corresponding residues on DPP9 have a different impact whereby the mutations decrease activity without changing dimerization. Thus the propeller loop seems to play a varying role in different DPPs.Structured summary of protein interactions:DPP-IV and DPP-IV physically interact by comigration in gel electrophoresis (View interaction: 1, 2, 3, 4)DPP9 and DPP9 bind by circular dichroism (View interaction)DPP-IV and DPP-IV bind by circular dichroism (View interaction: 1, 2, 3, 4, 5)DPP-IV and DPP-IV bind by cosedimentation in solution (View interaction: 1, 2, 3, 4, 5)ADA binds to DPP-IV by surface plasmon resonance (View interaction: 1, 2, 3, 4, 5, 6)DPP9 and DPP9 bind by cosedimentation in solution (View interaction) (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.