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

Autor: Lioe TS; Department of Biological Sciences, School of Science, Xi'an Jiaotong-Liverpool University, 111 Ren'ai Road, Suzhou, Jiangsu 215123, P. R. China., Xie Z; Department of Biological Sciences, School of Science, Xi'an Jiaotong-Liverpool University, 111 Ren'ai Road, Suzhou, Jiangsu 215123, P. R. China., Wu J; Department of Chemistry, School of Science, Xi'an Jiaotong-Liverpool University, 111 Ren'ai Road, Suzhou, Jiangsu 215123, P. R. China., Li W; Department of Biological Sciences, School of Science, Xi'an Jiaotong-Liverpool University, 111 Ren'ai Road, Suzhou, Jiangsu 215123, P. R. China., Sun L; Department of Biological Sciences, School of Science, Xi'an Jiaotong-Liverpool University, 111 Ren'ai Road, Suzhou, Jiangsu 215123, P. R. China., Feng Q; Department of Biological Sciences, School of Science, Xi'an Jiaotong-Liverpool University, 111 Ren'ai Road, Suzhou, Jiangsu 215123, P. R. China., Sekar R; Department of Biological Sciences, School of Science, Xi'an Jiaotong-Liverpool University, 111 Ren'ai Road, Suzhou, Jiangsu 215123, P. R. China., Tefsen B; Ronin Institute, Montclair, NJ 07043, USA.; Microbiology, Department of Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands., Ruiz-Carrillo D; European Molecular Biology Laboratory, Notkestraße 85, D-22607 Hamburg, Germany.
Jazyk: angličtina
Zdroj: Biological chemistry [Biol Chem] 2023 Jan 12; Vol. 404 (6), pp. 633-643. Date of Electronic Publication: 2023 Jan 12 (Print Publication: 2023).
DOI: 10.1515/hsz-2022-0265
Abstrakt: 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 P 1 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.
(© 2022 the author(s), published by De Gruyter, Berlin/Boston.)
Databáze: MEDLINE
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