X-ray structures of human furin in complex with competitive inhibitors

ACS Chemical Biology

Volumn 9, Issue 5, 2014, Pages 1113-1118

  Dahms, Sven O ^a   Hardes, Kornelia ^b   Becker, Gero L ^b   Steinmetzer, Torsten ^b   Brandstetter, Hans ^c   Than, Manuel E ^a  

^a FRITZ LIPMANN INSTITUTE   (Germany)

^b PHILIPPS UNIVERSITY MARBURG   (Germany)

^c UNIVERSITY OF SALZBURG   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME INHIBITOR; FURIN; FURIN INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; COMPETITIVE INHIBITION; CRYSTAL STRUCTURE; CRYSTALLIZATION; DRUG DESIGN; DRUG PROTEIN BINDING; DRUG PURIFICATION; DRUG STABILITY; DRUG SYNTHESIS; EMBRYO; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN STRUCTURE; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG EFFECTS; METABOLISM; MOLECULAR DOCKING; PROTEIN CONFORMATION; X RAY CRYSTALLOGRAPHY;

CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; FURIN; HUMANS; MOLECULAR DOCKING SIMULATION; PROTEIN CONFORMATION;

EID: 84900838688     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/cb500087x     Document Type: Article

References (32)

1. Siezen, R. J. and Leunissen, J. A. (1997) Subtilases: the superfamily of subtilisin-like serine proteases Protein Sci. 6, 501-523
2. Thomas, G. (2002) Furin at the cutting edge: from protein traffic to embryogenesis and disease Nat. Rev. Mol. Cell. Biol. 3, 753-766
3. Artenstein, A. W. and Opal, S. M. (2011) Proprotein convertases in health and disease N. Engl. J. Med. 365, 2507-2518
4. Seidah, N. G. and Prat, A. (2012) The biology and therapeutic targeting of the proprotein convertases Nat. Rev. 11, 367-383
5. Couture, F., DAnjou, F., and Day, R. (2011) On the cutting edge of proprotein convertase pharmacology: from molecular concepts to clinical applications Biomol. Concepts 2, 421-438
6. Zhu, J., Declercq, J., Roucourt, B., Ghassabeh, G. H., Meulemans, S., Kinne, J., David, G., Vermorken, A. J., Van de Ven, W. J., Lindberg, I., Muyldermans, S., and Creemers, J. W. (2012) Generation and characterization of non-competitive furin-inhibiting nanobodies Biochem. J. 448, 73-82
7. Lopez de Cicco, R., Bassi, D. E., Zucker, S., Seidah, N. G., and Klein-Szanto, A. J. (2005) Human carcinoma cell growth and invasiveness is impaired by the propeptide of the ubiquitous proprotein convertase furin Cancer Res. 65, 4162-4171
8. Coppola, J. M., Bhojani, M. S., Ross, B. D., and Rehemtulla, A. (2008) A small-molecule furin inhibitor inhibits cancer cell motility and invasiveness Neoplasia (N. Y., NY, U. S.) 10, 363-370
9. Hallenberger, S., Bosch, V., Angliker, H., Shaw, E., Klenk, H. D., and Garten, W. (1992) Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160 Nature 360, 358-361
10. Becker, G. L., Sielaff, F., Than, M. E., Lindberg, I., Routhier, S., Day, R., Lu, Y., Garten, W., and Steinmetzer, T. (2010) Potent inhibitors of furin and furin-like proprotein convertases containing decarboxylated P1 arginine mimetics J. Med. Chem. 53, 1067-1075
11. Sarac, M. S., Peinado, J. R., Leppla, S. H., and Lindberg, I. (2004) Protection against anthrax toxemia by hexa-D-arginine in vitro and in vivo Infection Immunity 72, 602-605
12. Shiryaev, S. A., Remacle, A. G., Ratnikov, B. I., Nelson, N. A., Savinov, A. Y., Wei, G., Bottini, M., Rega, M. F., Parent, A., Desjardins, R., Fugere, M., Day, R., Sabet, M., Pellecchia, M., Liddington, R. C., Smith, J. W., Mustelin, T., Guiney, D. G., Lebl, M., and Strongin, A. Y. (2007) Targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogens J. Biol. Chem. 282, 20847-20853
13. Henrich, S., Cameron, A., Bourenkov, G. P., Kiefersauer, R., Huber, R., Lindberg, I., Bode, W., and Than, M. E. (2003) The crystal structure of the proprotein processing proteinase furin explains its stringent specificity Nat. Struct. Biol. 10, 520-526
14. Holyoak, T., Wilson, M. A., Fenn, T. D., Kettner, C. A., Petsko, G. A., Fuller, R. S., and Ringe, D. (2003) 2.4 A resolution crystal structure of the prototypical hormone-processing protease Kex2 in complex with an Ala-Lys-Arg boronic acid inhibitor Biochemistry 42, 6709-6718
15. Becker, G. L., Lu, Y., Hardes, K., Strehlow, B., Levesque, C., Lindberg, I., Sandvig, K., Bakowsky, U., Day, R., Garten, W., and Steinmetzer, T. (2012) Highly potent inhibitors of proprotein convertase furin as potential drugs for treatment of infectious diseases J. Biol. Chem. 287, 21992-22003
16. Reeves, P. J., Callewaert, N., Contreras, R., and Khorana, H. G. (2002) Structure and function in rhodopsin: high-level expression of rhodopsin with restricted and homogeneous N-glycosylation by a tetracycline-inducible N-acetylglucosaminyltransferase I-negative HEK293S stable mammalian cell line Proc. Natl. Acad. Sci. U.S.A. 99, 13419-13424
17. Kuester, M., Becker, G. L., Hardes, K., Lindberg, I., Steinmetzer, T., and Than, M. E. (2011) Purification of the proprotein convertase furin by affinity chromatography based on PC-specific inhibitors Biol. Chem. 392, 973-981
18. Krissinel, E. and Henrick, K. (2004) Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions Acta Crystallogr. 60, 2256-2268
19. Henrich, S., Lindberg, I., Bode, W., and Than, M. E. (2005) Proprotein convertase models based on the crystal structures of furin and kexin: explanation of their specificity J. Mol. Biol. 345, 211-227
20. Creemers, J. W., Choquet, H., Stijnen, P., Vatin, V., Pigeyre, M., Beckers, S., Meulemans, S., Than, M. E., Yengo, L., Tauber, M., Balkau, B., Elliott, P., Jarvelin, M. R., Van Hul, W., Van Gaal, L., Horber, F., Pattou, F., Froguel, P., and Meyre, D. (2012) Heterozygous mutations causing partial prohormone convertase 1 deficiency contribute to human obesity Diabetes 61, 383-390
21. Than, M. E., Henrich, S., Bourenkov, G. P., Bartunik, H. D., Huber, R., and Bode, W. (2005) The endoproteinase furin contains two essential Ca2+ ions stabilizing its N-terminus and the unique S1 specificity pocket Acta Crystallogr. 61, 505-512
22. Zheng, H., Chordia, M. D., Cooper, D. R., Chruszcz, M., Muller, P., Sheldrick, G. M., and Minor, W. (2014) Validation of metal-binding sites in macromolecular structures with the CheckMyMetal web server Nat. Protoc. 9, 156-170
23. Wheatley, J. L. and Holyoak, T. (2007) Differential P1 arginine and lysine recognition in the prototypical proprotein convertase Kex2 Proc. Natl. Acad. Sci. U.S.A. 104, 6626-6631
24. Wells, C. M. and Di Cera, E. (1992) Thrombin is a Na(+)-activated enzyme Biochemistry 31, 11721-11730
25. Di Cera, E. (2004) Thrombin: a paradigm for enzymes allosterically activated by monovalent cations C. R. Biol. 327, 1065-1076
26. Gros, P., Kalk, K. H., and Hol, W. G. (1991) Calcium binding to thermitase. Crystallographic studies of thermitase at 0, 5, and 100 mM calcium J. Biol. Chem. 266, 2953-2961
27. Tian, S., Huang, Q., Fang, Y., and Wu, J. (2011) FurinDB: A database of 20-residue furin cleavage site motifs, substrates and their associated drugs Int. J. Mol. Sci. 12, 1060-1065
28. Aricescu, A. R., Lu, W., and Jones, E. Y. (2006) A time-and cost-efficient system for high-level protein production in mammalian cells Acta Crystallogr. 62, 1243-1250
29. Mueller, U., Darowski, N., Fuchs, M. R., Forster, R., Hellmig, M., Paithankar, K. S., Puhringer, S., Steffien, M., Zocher, G., and Weiss, M. S. (2012) Facilities for macromolecular crystallography at the Helmholtz-Zentrum Berlin J. Synchrotron Radiat. 19, 442-449
30. Kabsch, W. (2010) Xds Acta Crystallogr. 66, 125-132
31. Emsley, P., Lohkamp, B., Scott, W. G., and Cowtan, K. (2010) Features and development of Coot Acta Crystallogr. 66, 486-501
32. Brunger, A. T. (2007) Version 1.2 of the Crystallography and NMR system Nat. Protoc. 2, 2728-2733