The Mycobacterium tuberculosis prolyl dipeptidyl peptidase cleaves the N-terminal peptide of the immunoprotein CXCL-10.

IF 2.9 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trillion Surya Lioe, Ziwen Xie, Jianfang Wu, Wenlong Li, Li Sun, Qiaoli Feng, Raju Sekar, Boris Tefsen, David Ruiz-Carrillo
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引用次数: 0

Abstract

Dipeptidyl peptidases constitute a class of non-classical serine proteases that regulate an array of biological functions, making them pharmacologically attractive enzymes. With this work, we identified and characterized a dipeptidyl peptidase from Mycobacterium tuberculosis (MtDPP) displaying a strong preference for proline residues at the P1 substrate position and an unexpectedly high thermal stability. MtDPP was also characterized with alanine replacements of residues of its active site that yielded, for the most part, loss of catalysis. We show that MtDPP catalytic activity is inhibited by well-known human DPP4 inhibitors. Using MALDI-TOF mass spectrometry we also describe that in vitro, MtDPP mediates the truncation of the C-X-C motif chemokine ligand 10, indicating a plausible role in immune modulation for this mycobacterial enzyme.

结核分枝杆菌脯氨酸二肽基肽酶可切割免疫蛋白CXCL-10的n端肽。
二肽基肽酶是一类非经典丝氨酸蛋白酶,可调节一系列生物学功能,使其成为具有药理吸引力的酶。通过这项工作,我们从结核分枝杆菌(MtDPP)中鉴定并表征了一种二肽基肽酶,该酶在P1底物位置表现出对脯氨酸残基的强烈偏好,并且具有意想不到的高热稳定性。MtDPP还具有丙氨酸取代其活性位点残基的特征,这在很大程度上导致了催化作用的丧失。我们发现MtDPP的催化活性被众所周知的人类DPP4抑制剂所抑制。使用MALDI-TOF质谱,我们还描述了在体外,MtDPP介导C-X-C基序趋化因子配体10的截断,表明该分枝杆菌酶在免疫调节中的合理作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biological Chemistry
Biological Chemistry 生物-生化与分子生物学
CiteScore
7.20
自引率
0.00%
发文量
63
审稿时长
4-8 weeks
期刊介绍: Biological Chemistry keeps you up-to-date with all new developments in the molecular life sciences. In addition to original research reports, authoritative reviews written by leading researchers in the field keep you informed about the latest advances in the molecular life sciences. Rapid, yet rigorous reviewing ensures fast access to recent research results of exceptional significance in the biological sciences. Papers are published in a "Just Accepted" format within approx.72 hours of acceptance.
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