A Computational Model for Predicting ADAM17 Substrate Specificity

Abstract:

Tumor necrosis factor-alpha converting enzyme (TACE) is a membrane-anchored protein that releases the soluble forms of many proteins by a process called ectodomain shedding. TACE has been considered as a potential target in a lot of diseases in autoimmune diseases and in cancers recently. In spite a lot of protein substrates have been found these years for TACE, the substrate selection of TACE is still not known. In this paper, a TACE-peptide complex was constructed, and used for the prediction of substrate sequences and cleavage sites. The result could be useful for understanding the substrate specificity of TACE, and designing better TACE inhibitors in future.

• Periodical: Advanced Materials Research (Volume 740)
• Pages: 525-529
• DOI: https://doi.org/10.4028/www.scientific.net/AMR.740.525
• Online since: August 2013
• Authors: Liu Sen, Dong Pei, Song Liu, Xiao Hong Ma
• Keywords: ADAM17, Protein Prediction, Substrate Specificity, TACE

References

[1] K. P. Fong, C. Barry, A. N. Tran, E. A. Traxler, K. M. Wannemacher, H. Y. Tang, K. D. Speicher, I. A. Blair, D. W. Speicher, T. Grosser, and L. F. Brass, Deciphering the human platelet sheddome, Blood, vol. 117, pp. e15-26, Jan 6 (2011).

DOI: 10.1182/blood-2010-05-283838

[2] P. Saftig and K. Reiss, The "A Disintegrin And Metalloproteases" ADAM10 and ADAM17: novel drug targets with therapeutic potential?, European journal of cell biology, vol. 90, pp.527-35, Jun-Jul (2011).

DOI: 10.1016/j.ejcb.2010.11.005

[3] M. Gooz, ADAM-17: the enzyme that does it all, Crit Rev Biochem Mol Biol, vol. 45, pp.146-69, Apr (2010).

[4] P. E. Gonzales, A. Solomon, A. B. Miller, M. A. Leesnitzer, I. Sagi, and M. E. Milla, Inhibition of the tumor necrosis factor-alpha-converting enzyme by its pro domain, J Biol Chem, vol. 279, pp.31638-45, Jul 23 (2004).

DOI: 10.1074/jbc.m401311200

[5] J. Scheller, A. Chalaris, C. Garbers, and S. Rose-John, ADAM17: a molecular switch to control inflammation and tissue regeneration, Trends in immunology, vol. 32, pp.380-7, Aug (2011).

DOI: 10.1016/j.it.2011.05.005

[6] M. S. Bahia and O. Silakari, Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders, Chem Biol Drug Des, vol. 75, pp.415-43, May (2010).

DOI: 10.1111/j.1747-0285.2010.00950.x

[7] P. R. Murumkar, S. DasGupta, S. R. Chandani, R. Giridhar, and M. R. Yadav, Novel TACE inhibitors in drug discovery: a review of patented compounds, Expert Opin Ther Pat, vol. 20, pp.31-57, Jan (2010).

DOI: 10.1517/13543770903465157

[8] S. DasGupta, P. R. Murumkar, R. Giridhar, and M. R. Yadav, Current perspective of TACE inhibitors: a review, Bioorg Med Chem, vol. 17, pp.444-59, Jan 15 (2009).

DOI: 10.1016/j.bmc.2008.11.067

[9] A. Chalaris, N. Adam, C. Sina, P. Rosenstiel, J. Lehmann-Koch, P. Schirmacher, D. Hartmann, J. Cichy, O. Gavrilova, S. Schreiber, T. Jostock, V. Matthews, R. Hasler, C. Becker, M. F. Neurath, K. Reiss, P. Saftig, J. Scheller, and S. Rose-John, Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice, The Journal of experimental medicine, vol. 207, pp.1617-24, Aug 2 (2010).

DOI: 10.1084/jem.20092366

[10] K. Brandl, L. Sun, C. Neppl, O. M. Siggs, S. M. Le Gall, W. Tomisato, X. Li, X. Du, D. N. Maennel, C. P. Blobel, and B. Beutler, MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands, Proc Natl Acad Sci U S A, vol. 107, pp.19967-72, Nov 16 (2010).

DOI: 10.1073/pnas.1014669107

[11] K. Maskos, C. Fernandez-Catalan, R. Huber, G. P. Bourenkov, H. Bartunik, G. A. Ellestad, P. Reddy, M. F. Wolfson, C. T. Rauch, B. J. Castner, R. Davis, H. R. Clarke, M. Petersen, J. N. Fitzner, D. P. Cerretti, C. J. March, R. J. Paxton, R. A. Black, and W. Bode, Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme, Proc Natl Acad Sci U S A, vol. 95, pp.3408-12, Mar 31 (1998).

DOI: 10.1073/pnas.95.7.3408

[12] B. Raveh, N. London, L. Zimmerman, and O. Schueler-Furman, Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors, PLoS One, vol. 6, p. e18934, (2011).

DOI: 10.1371/journal.pone.0018934

[13] C. A. Smith and T. Kortemme, Backrub-like backbone simulation recapitulates natural protein conformational variability and improves mutant side-chain prediction, Journal of molecular biology, vol. 380, pp.742-56, Jul 18 (2008).

DOI: 10.1016/j.jmb.2008.05.023

[14] C. A. Smith and T. Kortemme, Structure-based prediction of the peptide sequence space recognized by natural and synthetic PDZ domains, Journal of molecular biology, vol. 402, pp.460-74, Sep 17 (2010).

DOI: 10.1016/j.jmb.2010.07.032

[15] G. Kapp, S. Liu, D. Wong, A. Reményi, B. Yeh, J. Fraser, J. Taunton, W. Lim, and T. Kortemme, Control of protein signaling using a computationally designed GTPase/GEF orthogonal pair, Proc Natl Acad Sci U S A, submitted for publication.

DOI: 10.1073/pnas.1114487109

[16] C. I. Caescu, G. R. Jeschke, and B. E. Turk, Active-site determinants of substrate recognition by the metalloproteinases TACE and ADAM10, Biochem J, vol. 424, pp.79-88, Nov 15 (2009).

DOI: 10.1042/bj20090549

[17] M. H. Lambert, R. K. Blackburn, T. D. Seaton, D. B. Kassel, D. S. Kinder, M. A. Leesnitzer, D. M. Bickett, J. R. Warner, M. W. Andersen, J. G. Badiang, D. J. Cowan, M. D. Gaul, K. G. Petrov, M. H. Rabinowitz, R. W. Wiethe, J. D. Becherer, D. L. McDougald, D. L. Musso, R. C. Andrews, and M. L. Moss, Substrate specificity and novel selective inhibitors of TNF-alpha converting enzyme (TACE) from two-dimensional substrate mapping, Comb Chem High Throughput Screen, vol. 8, pp.327-39, Jun (2005).

DOI: 10.2174/1386207054020840