Crystal structures of TAFI elucidate the inactivation mechanism of activated TAFI: A novel mechanism for enzyme autoregulation

Blood

Volumn 112, Issue 7, 2008, Pages 2803-2809

  Marx, Pauline F ^a   Brondijk, T Harma C ^b   Plug, Tom ^a   Romijn, Roland A ^c   Hemrika, Wieger ^c   Meijers, Joost C M ^a   Huizinga, Eric G ^b  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

^b UTRECHT UNIVERSITY   (Netherlands)

^c UTRECHT UNIVERSITY   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME PRECURSOR; THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR; CARBOXYPEPTIDASE; ENZYME INHIBITOR; PROTEIN PRECURSOR;

ARTICLE; AUTOREGULATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLIZATION; ENZYME ACTIVE SITE; ENZYME CONFORMATION; ENZYME INACTIVATION; ENZYME STABILITY; GENE MUTATION; PRIORITY JOURNAL; BIOLOGICAL MODEL; CELL LINE; CHEMISTRY; ENZYME ACTIVATION; GENETICS; HUMAN; METABOLISM; MUTATION; PROTEIN SECONDARY STRUCTURE; X RAY CRYSTALLOGRAPHY;

CARBOXYPEPTIDASE U; CARBOXYPEPTIDASES; CELL LINE; CRYSTALLOGRAPHY, X-RAY; ENZYME ACTIVATION; ENZYME INHIBITORS; HUMANS; MODELS, BIOLOGICAL; MUTATION; PROTEIN PRECURSORS; PROTEIN STRUCTURE, SECONDARY;

EID: 53449101060     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2008-03-146001     Document Type: Article

References (36)

1. Bouma BN, Marx PR Mosnier LO, Meijers JCM. Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B. procarboxypeptidase R, procarboxypeptidase U). Thromb Res. 2001;101:329-354.
2. Marx PR Thrombin-activatable fibrinolysis inhibitor. Curr Medic Chem. 2004;11:2335-2348.
3. BinetteTM, Taylor FB, Jr., Peer G, Bajzar L. Thrombin-thrombomodulin connects coagulation and fibrinolysis: more than an in vitro phenomenon. Blood. 2007;110:3168-3175.
4. Boffa MB, Koschinsky ML. Curiouser and curiouser: Recent advances in measurement of thrombin-activatable fibirinolysis inhibitor (TAFI) and in understanding its molecular genetics, gene regulation, and biological roles. Clin Biochem. 2007;40:431-442.
5. Bouma BN, Mosnier LO. Thrombin activatable fibrinolysis inhibitor (TAFI) at the interface between coagulation and fibrinolysis. Pathophysiol Haemost Thromb. 2003;33:375-381.
6. Boffa MB, Bell R, Stevens WK, Nesheim ME. Roles of thermal instability and proteolytic cleavage in regulation of activated thrombin-activable fibrinolysis inhibitor. J Biol Chem. 2000;275: 12868-12878.
7. Marx PF, Hackeng TM, Dawson PE, et al. Inactivation of active thrombin-activable fibrinolysis inhibitor takes place by a process that involves conformational instability rather than proteolytic cleavage. J Biol Chem. 2000;275:12410-12415.
8. Leurs J, Nerme V, Sim Y, Hendriks D. Carboxypeptidase U (TAFIa) prevents lysis from proceeding into the propagation phase through a threshold-dependent mechanism. J Thromb Haemost. 2004;2:416-423.
9. Schneider M, Boffa M, Stewart R, et al. Two naturally occurring variants of TAPI (Thr-325 and lle-325) differ substantially with respect to thermal stability and antifibrinolytic activity of the enzyme. J Biol Chem. 2002;277:1021-1030.
10. Walker JB, Bajzar L. The intrinsic threshold of the fibrinolytic system is modulated by basic carboxypeptidases, but the magnitude of the antifibrinolytic effect of activated thrombin-activable fibrinolysis inhibitor is masked by its instability. J Biol Chem. 2004;279:27896-27904.
11. Garcia-Castellanos R, Bonet-Figueredo R, Pallares I, et al. Detailed molecular comparison between the inhibition mode of A/B-type carboxypeptidases in the zymogen state and by the endogenous inhibitor latexin. Cell Mol Life Sci. 2005;62:1996-2014.
12. Garcia-Saez I, Reveller D, Vendrell J, Aviles FX, Coll M. The three-dimensional structure of human procarboxypeptidase A2, Deciphering the basis of the inhibition, activation and intrinsic activity of the zymogen. EMBO J. 1997;16:6906-6913.
13. Pereira PJB, Segura-Martin S, Oliva B, et al. Human procarboxypeptidase B: Three-dimensional structure and implications for thrombinactivatable fibrinolysis inhibitor (TAFI). J Mol Biol. 2002;321:537-547.
14. Marx PF, Havik SR, Bouma BN, Meijers JCM. Role of isoleucine residues 182 and 183 in thrombin activatable fibrinolysis inhibitor. J Thromb Haemost. 2005;3:1293-1300.
15. Wang W, Hendriks DF, Scharpe SS. Carboxypeptidase U, a plasma carboxypeptidase with high affinity for plasminogen. J Biol Chem. 1994;269: 15937-15944.
16. Schneider M, Nesheim M. Reversible inhibitors of TAFIa can both promote and inhibit fibrinolysis. J Thromb Haemost. 2003;1:147-154.
17. Walker JB, Hughes B, James I, et al. Stabilization versus inhibition of TAFIa by competitive inhibitors in vitro. J Biol Chem. 2003;278:8913-8921.
18. Ceresa E, Van de BK, Peeters M, et al. Generation of a stable activated thrombin activable fibrinolysis inhibitor variant. J Biol Chem. 2006;281: 15878-15883.
19. Ceresa E, Peeters M, Declerck PJ, Gils A. Announcing a TAFIa mutant with a 180-fold increased half-life and concomitantly a strongly increased antifibrinolytic potential. J Thromb Haemost. 2007;5:418-420.
20. Knecht W, Willemse J, Stenhamre H, et al. Limited mutagenesis increases the stability of human carboxypeptidase U (TAFIaJ and demonstrates the importance of CPU stability over proCPU concentration in down-regulating fibrinolysis. FEBS J. 2006;273:778-792.
21. Barash S, Wang W, Shi Y. Human secretory signal peptide description by hidden Markov model and generation of a strong artificial signal peptide for secreted protein expression. Biochem Biophys Res Commun. 2002;294:835-842.
22. Reeves PJ, Callewaert N, Contreras R, Khorana HG. Structure and function in rhodopsin: highlevel expression of rhodopsin with restricted and homogeneous N-glycosylation by a tetracyclineinducible N-acetylglucosaminyltransferase I-negative HEK293S stable mammalian cell line. Proc Natl Acad Sci U S A. 2002;99:13419-13424.
23. Durocher Y. Perret S, Kamen A. High-level and high-throughput recombinant protein production by transient transfection of suspension-growing human 293-EBNA1 cells. Nucleic Acids Res. 2002;30:E9.
24. Kabsch W. Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants. J Appl Crystallogr. 1993;26:795-800.
25. Read RJ. Pushing the boundaries of molecular replacement with maximum likelihood. Acta Crystallogr D Biol Crystallogr. 2001;57:1373-1382.
26. Terwilliger TC. Maximum-likelihood density modification. Acta Crystallogr D Biol Crystallogr. 2000; 56:965-972.
27. The CCP4 suite: programs for protein crystallography. Acta Crystallogr D. 1994;50:760-763.
28. Emsley P, Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr D. 2004; 60:2126-2132.
29. Laskowski RA, MacArthur MW, Moss DS, Thornton JM. PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr. 1993;26283-291.
30. Petrek M, Otyepka M, Banas P, et al. CAVER: a new tool to explore routes from protein clefts, pockets and cavities. BMC Bioinformatics. 2006; 7:316.
31. Valnickova Z, Christensen T, Skottrup P, et al. Post-translational modifications of human thrombin-activatable fibrinolysis inhibitor (TAFI): Evidence for a large shift in the isoelectric point and reduced solubility upon activation. Biochemistry. 2006;45:1525-1535.
32. Willemse JL, Polla M, Hendriks DF. The intrinsic enzymatic activity of plasma procarboxypeptidase U (TAFI) can interfere with plasma carboxypeptidase N assays. Anal Biochem. 2006; 356:157-159.
33. Valnickova Z, Thogersen IB, Potempa J, Enghild JJ. Thrombin-activable fibrinolysis inhibitor (TAFI) zymogen is an active carboxypeptidase. J Biol Chem. 2007;282:3066-3076.
34. Rees DC, Lipscomb WN. Crystallographic studies on apocarboxypeptidase A and the complex with glycyl-L-tyrosine. Proc Natl Acad Sci U S A. 1983;80:7151-7154.
35. Aloy P, Companys V, Vendrell J, et al. The crystal structure of the inhibitor-complexed carboxypeptidase D domain II and the modeling of regulatory carboxypeptidases. J Biol Chem. 2001;276: 16177-16184.
36. Ceresa E, De Maeyer M, JonckheerA, et al. Comparative evaluation of stable TAFIa variants: importance of alpha-helix 9 and beta-sheet 11 for TAFIa (in)stability. J Thromb Haemost. 2007;5: 2105-2112.