TY - JOUR
T1 - The Mycobacterium tuberculosis prolyl dipeptidyl peptidase cleaves the N-terminal peptide of the immunoprotein CXCL-10
AU - Lioe, Trillion Surya
AU - Xie, Ziwen
AU - Wu, Jianfang
AU - Li, Wenlong
AU - Sun, Li
AU - Feng, Qiaoli
AU - Sekar, Raju
AU - Tefsen, Boris
AU - Ruiz-Carrillo, David
N1 - Funding Information:
Research funding: The authors would like to thank the Department of Biological Sciences, Xi’an Jiaotong-Liverpool University (XJTLU) for providing laboratory facilities and funding support. DRC would like to acknowledge the Research Development Fund RDF-16-01-18 for financial support. R.S. would like to acknowledge the Key Program Special Fund in XJTLU (Grant No. KSF-E-20) and Continuous Support Fund (RDF-SP-88) for financial support.
Publisher Copyright:
© 2022 the author(s), published by De Gruyter, Berlin/Boston 2022.
PY - 2023/1/12
Y1 - 2023/1/12
N2 - 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.
AB - 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.
KW - CXCL-10
KW - DPP4
KW - immune modulation
KW - post-proline
KW - prolyl oligopeptidase
KW - thermostable
UR - http://www.scopus.com/inward/record.url?scp=85146216129&partnerID=8YFLogxK
U2 - 10.1515/hsz-2022-0265
DO - 10.1515/hsz-2022-0265
M3 - Article
C2 - 36632703
AN - SCOPUS:85146216129
SN - 1431-6730
VL - 404
SP - 633
EP - 643
JO - Biological Chemistry
JF - Biological Chemistry
IS - 6
ER -
