The <i>Mycobacterium tuberculosis</i> prolyl dipeptidyl peptidase cleaves the N-terminal peptide of the immunoprotein CXCL-10-Reference-Cited by-同舟云学术

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

Published:2023-01-12 Issue:6 Volume:404 Page:633-643
ISSN:1431-6730
Container-title:Biological Chemistry
language:en
Short-container-title:

Author:

Lioe Trillion Surya¹^ORCID,Xie Ziwen¹^ORCID,Wu Jianfang²,Li Wenlong¹,Sun Li¹,Feng Qiaoli¹,Sekar Raju¹^ORCID,Tefsen Boris³⁴^ORCID,Ruiz-Carrillo David⁵^ORCID

Affiliation:

1. Department of Biological Sciences, School of Science , Xi’an Jiaotong-Liverpool University , 111 Ren’ai Road , Suzhou , Jiangsu 215123 , P. R. China

2. Department of Chemistry, School of Science , Xi’an Jiaotong-Liverpool University , 111 Ren’ai Road , Suzhou , Jiangsu 215123 , P. R. China

3. Ronin Institute , Montclair , NJ 07043 , USA

4. Microbiology, Department of Biology, Utrecht University , Padualaan 8, 3584 CH Utrecht , Netherlands

5. European Molecular Biology Laboratory , Notkestraße 85, D-22607 Hamburg , Germany

Abstract

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.

Funder

XJTLU Continuous Support Fund

XJTLU Research Development Fund

XJTLU Key Program Special Fund

Publisher

Walter de Gruyter GmbH

Subject

Clinical Biochemistry,Molecular Biology,Biochemistry

Link

https://www.degruyter.com/document/doi/10.1515/hsz-2022-0265/pdf

Reference55 articles.

1. Abbott, C.A., McCaughan, G.W., and Gorrell, M.D. (1999). Two highly conserved glutamic acid residues in the predicted beta propeller domain of dipeptidyl peptidase IV are required for its enzyme activity. FEBS Lett. 458: 278–284, https://doi.org/10.1016/s0014-5793(99)01166-7.

2. Aertgeerts, K., Ye, S., Tennant, M.G., Kraus, M.L., Rogers, J., Sang, B.C., Skene, R.J., Webb, D.R., and Prasad, G.S. (2004). Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide reveals details on substrate specificity and tetrahedral intermediate formation. Protein Sci. 13: 412–421, https://doi.org/10.1110/ps.03460604.

3. Bjelke, J.R., Christensen, J., Branner, S., Wagtmann, N., Olsen, C., Kanstrup, A.B., and Rasmussen, H.B. (2004). Tyrosine 547 constitutes an essential part of the catalytic mechanism of dipeptidyl peptidase IV. J. Biol. Chem. 279: 34691–34697, https://doi.org/10.1074/jbc.m405400200.

4. Bjelke, J.R., Christensen, J., Nielsen, P.F., Branner, S., Kanstrup, A.B., Wagtmann, N., and Rasmussen, H.B. (2006). Dipeptidyl peptidases 8 and 9: specificity and molecular characterization compared with dipeptidyl peptidase IV. Biochem. J. 396: 391–399, https://doi.org/10.1042/bj20060079.

5. Blauenfeldt, T., Petrone, L., Del Nonno, F., Baiocchini, A., Falasca, L., Chiacchio, T., Bondet, V., Vanini, V., Palmieri, F., Galluccio, G., et al.. (2018). Interplay of DDP4 and IP-10 as a potential mechanism for cell recruitment to tuberculosis lesions. Front. Immunol. 9: 1456, https://doi.org/10.3389/fimmu.2018.01456.