The Vitamin K oxidoreductase is a multimer that efficiently reduces Vitamin K epoxide to hydroquinone to allow Vitamin K-dependent protein carboxylation

Journal of Biological Chemistry

Volumn 288, Issue 44, 2013, Pages 31556-31566

  Rishavy, Mark A ^a   Hallgren, Kevin W ^a   Wilson, Lee A ^a   Usubalieva, Aisulu ^a   Runge, Kurt W ^a   Berkner, Kathleen L ^a  

^a LERNER RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIRECT DETECTION; DOMINANT NEGATIVE; FUNCTIONAL PROPERTIES; HETERODIMERS; INACTIVE MUTANTS; INSECT CELLS; MOST LIKELY; OXIDOREDUCTASES;

BIOMINERALIZATION; DIMERS; PHENOLS; PROTEINS;

CARBOXYLATION;

CALCIUM; DIMER; EPOXIDE; HETERODIMER; HOMODIMER; HYDROQUINONE; MEMBRANE PROTEIN; OXIDOREDUCTASE; POLYMER; VITAMIN K GROUP; WARFARIN;

ALLELE; APOPTOSIS; ARTICLE; CALCIFICATION; CALCIUM HOMEOSTASIS; CARBOXYLATION; ENDOPLASMIC RETICULUM; GROWTH REGULATION; HEMOSTASIS; HUMAN; IMMUNOPRECIPITATION; IN VITRO STUDY; OXIDATION; PRIORITY JOURNAL; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN PURIFICATION; SIGNAL TRANSDUCTION; WILD TYPE;

ENZYME MECHANISMS; MEMBRANE ENZYMES; PROTEIN CARBOXYLATION; REDUCTASE; VITAMINS AND COFACTORS;

AMINO ACID SUBSTITUTION; ANTICOAGULANTS; DRUG RESISTANCE; HEK293 CELLS; HUMANS; HYDROQUINONES; MUTATION, MISSENSE; OXIDATION-REDUCTION; PROTEIN MULTIMERIZATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; VITAMIN K; VITAMIN K EPOXIDE REDUCTASES; WARFARIN;

EID: 84887060047     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.497297     Document Type: Article

References (35)

1. Berkner, K. L. (2005) The vitamin K-dependent carboxylase. Annu. Rev. Nutr. 25, 127-149 (Pubitemid 41208997)
2. Berkner, K. L. (2008) Vitamin K-dependent carboxylation. Vitam. Horm. 78, 131-156
3. Au, N., and Rettie, A. E. (2008) Pharmacogenomics of 4-hydroxycoumarin anticoagulants. Drug Metab. Rev. 40, 355-375 (Pubitemid 352000950)
4. Dutton, R. J., Boyd, D., Berkmen, M., and Beckwith, J. (2008) Bacterial species exhibit diversity in their mechanisms and capacity for protein disulfide bond formation. Proc. Natl. Acad. Sci. U.S.A. 105, 11933-11938
5. Goodstadt, L., and Ponting, C. P. (2004) Vitamin K epoxide reductase: homology, active site and catalytic mechanism. Trends Biochem. Sci. 29, 289-292 (Pubitemid 38968759)
6. Tie, J. K., and Jin., D. Y., and Stafford, D. W. (2012) Mycobacterium tuberculosis vitamin K epoxide reductase homologue supports vitamin K-dependent carboxylation in mammalian cells. Antioxid. Redox. Signal. 16, 329-338
7. Singh, A. K., Bhattacharyya-Pakrasi, M., and Pakrasi, H. B. (2008) Identification of an atypical membrane protein involved in the formation of protein disulfide bonds in oxygenic photosynthetic organisms. J. Biol. Chem. 283, 15762-15770
8. Li, W., Schulman, S., Dutton, R. J., Boyd, D., Beckwith, J., and Rapoport, T. A. (2010) Structure of a bacterial homologue of vitamin K epoxide reductase. Nature 463, 507-512
9. Fasco, M. J., and Principe., L. M., Walsh, W. A., and Friedman, P. A. (1983) Warfarin inhibition of vitamin K 2, 3-epoxide reductase in rat liver microsomes. Biochemistry 22, 5655-5660 (Pubitemid 14212084)
10. Whitlon, D. S., and Sadowski., J. A., and Suttie, J. W. (1978) Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry 17, 1371-1377 (Pubitemid 8330368)
11. Rost, S., Fregin, A., Hünerberg, M., Bevans, C. G., Müller, C. R., and Oldenburg, J. (2005) Site-directed mutagenesis of coumarin-type anticoagulant-sensitive VKORC1: evidence that highly conserved amino acids define structural requirements for enzymatic activity and inhibition by warfarin. Thromb. Haemost. 94, 780-786 (Pubitemid 41489237)
12. Wajih, N., Sane, D. C, Hutson, S. M., and Wallin, R. (2005) Engineering of a recombinant vitamin K-dependent gamma-carboxylation system with enhanced γ-carboxyglutamic acid forming capacity: evidence for a functional CXXC redox center in the system. J. Biol. Chem. 280, 10540-10547 (Pubitemid 40395914)
13. Jin, D. Y., and Tie., J. K., and Stafford, D. W. (2007) The conversion of vitamin K epoxide to vitamin K quinone and vitamin K quinone to vitamin K hydroquinone uses the same active site cysteines. Biochemistry 46, 7279-7283 (Pubitemid 46974001)
14. Rost, S., Fregin, A., Ivaskevicius, V., Conzelmann, E., Hörtnagel, K., Pelz, H. J., Lappegard, K., Seifried, E., Scharrer, I., Tuddenham, E. G., Müller, C. R., Strom, T. M., and Oldenburg, J. (2004) Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 427, 537-541 (Pubitemid 38209110)
15. Li, T., and Chang., C. Y., Jin, D. Y., Lin, P. J., Khvorova, A., and Stafford, D. W. (2004) Identification of the gene for vitamin K epoxide reductase. Nature 427, 541-544 (Pubitemid 38209111)
16. Rishavy, M. A., Usubalieva, A., Hallgren, K. W., and Berkner, K. L. (2011) Novel insight into the mechanism of the vitamin K oxidoreductase (VKOR): electron relay through Cys43 and Cys51 reduces VKOR to allow vitamin K reduction and facilitation of vitamin K-dependent protein carboxylation. J. Biol. Chem. 286, 7267-7278
17. Tie, J. K., and Jin., D. Y., Straight, D. L., and Stafford, D. W. (2011) Functional study of the vitamin K cycle in mammalian cells. Blood 117, 2967-2974
18. Westhofen, P., Watzka, M., Marinova, M., Hass, M., Kirfel, G., Müller, J., Bevans, C. G., Müller, C. R., and Oldenburg, J. (2011) Human vitamin K 2, 3-epoxide reductase complex subunit 1-like 1 (VKORC1L1) mediates vitamin K-dependent intracellular antioxidant function. J. Biol. Chem. 286, 15085-15094
19. Fasco, M. J., and Principe, L. M. (1982) Vitamin K1 hydroquinone formation catalyzed by DT-diaphorase. Biochem. Biophys. Res. Commun. 104, 187-192 (Pubitemid 12146297)
20. Chu, P. H., and Huang., T. Y., Williams, J., and Stafford, D. W. (2006) Purified vitamin K epoxide reductase alone is sufficient for conversion of vitamin K epoxide to vitamin K and vitamin K to vitamin KH2. Proc. Natl. Acad. Sci. U.S.A. 103, 19308-19313 (Pubitemid 46026028)
21. Hallgren, K. W., Qian, W., Yakubenko, A. V., and Runge., K. W., and Berkner, K. L. (2006) r-VKORC1 expression in factor IX BHK cells increases the extent of factor IX carboxylation but is limited by saturation of another carboxylation component or by a shift in the rate-limiting step. Biochemistry 45, 5587-5598 (Pubitemid 43673189)
22. Berkner, K. L., and McNally, B. A. (1997) Purification of vitamin K-dependent carboxylase from cultured cells. Methods Enzymol. 282, 313-333 (Pubitemid 27412785)
23. Rishavy, M. A., and Berkner, K. L. (2008) Insight into the coupling mechanism of the vitamin K-dependent carboxylase: mutation of histidine 160 disrupts glutamic acid carbanion formation and efficient coupling of vitamin K epoxidation to glutamic acid carboxylation. Biochemistry 47, 9836-9846
24. Davidson, K. W., and Sadowski, J. A. (1997) Determination of vitamin K compounds in plasma or serum by high-performance liquid chromatography using postcolumn chemical reduction and fluorimetric detection. Methods Enzymol. 282, 408-421 (Pubitemid 27412792)
25. Fieser, L. F., Tishler, M., and Sampson, W. L. (1941) Vitamin K activity and structure. J. Biol. Chem. 137, 659-692
26. Berkner, K. L., and Pudota, B. N. (1998) Vitamin K-dependent carboxylation of the carboxylase. Proc. Natl. Acad. Sci. U.S.A. 95, 466-471 (Pubitemid 28083766)
27. Rishavy, M. A., and Hallgren., K. W., and Berkner, K. L. (2011) The vitamin K-dependent carboxylase generates γ-carboxylated glutamates by using CO2 to facilitate glutamate deprotonation in a concerted mechanism that drives catalysis. J. Biol. Chem. 286, 44821-44832
28. Roth, D. A., Rehemtulla, A., Kaufman, R. J., and Walsh., C. T., Furie, B., and Furie, B. C. (1993) Expression of bovine vitamin K-dependent carboxylase activity in baculovirus-infected insect cells. Proc. Natl. Acad. Sci. U.S.A. 90, 8372-8376 (Pubitemid 23277670)
29. Knobloch, J. E., and Suttie, J.W. (1987) Vitamin K-dependent carboxylase. Control of enzyme activity by the propeptide: region of factor X. J. Biol. Chem. 262, 15334-15337
30. Sugiura, I., Furie, B., Walsh, C. T., and Furie, B. C. (1997) Propeptide and glutamate-containing substrates bound to the vitamin K-dependent carboxylase convert its vitamin K epoxidase function from an inactive to an active state. Proc. Natl. Acad. Sci. U.S.A. 94, 9069-9074
31. Hallgren, K. W., and Hommema., E. L., McNally, B. A., and Berkner, K. L. (2002) Carboxylase overexpression impairs factor IX secretion: implications for the release of vitamin K-dependent proteins. Biochemistry 41, 15045-15055 (Pubitemid 35470684)
32. Sun, Y. M., and Jin., D. Y., Camire, R. M., and Stafford, D. W. (2005) Vitamin K epoxide reductase significantly improves carboxylation in a cell line overexpressing factor X. Blood 106, 3811-3815 (Pubitemid 41739017)
33. Tie, J. K., and Jin., D. Y., and Stafford, D. W. (2012) Human vitamin K epoxide reductase and its bacterial homologue have different membrane topologies and reaction mechanisms. J. Biol. Chem. 287, 33945-33955
34. Tie, J. K., Nicchitta, C., von Heijne, G., and Stafford, D. W. (2005) Membrane topology mapping of vitamin K epoxide reductase by in vitro translation/cotranslocation. J. Biol. Chem. 280, 16410-16416 (Pubitemid 40616771)
35. Stenina, O., and Pudota., B. N., McNally, B. A., Hommema, E. L., and Berkner, K. L. (2001) Tethered processivity of the vitamin K-dependent carboxylase: factor IX is efficiently modified in a mechanism which distinguishes Gla's from Glu's and which accounts for comprehensive carboxylation in vivo. Biochemistry 40, 10301-10309 (Pubitemid 32800137)