Vitamin K-Dependent Carboxylase and Vitamin K Epoxide Reductase

2009 ◽  
pp. 63-91
Keyword(s):  
Vitamin K ◽  
Vitamin K Epoxide Reductase ◽  
Epoxide Reductase

Comparison of vitamin K1 and K2 kinetics of vitamin K epoxide reductase C1

2008 ◽  
Vol 28 (S 01) ◽  
pp. S106-S106
Author(s):  
P. Westhofen ◽  
M. Watzka ◽  
M. Hass ◽  
C. Müller-Reible ◽  
D. Lütjohann ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K1 ◽  
Vitamin K Epoxide Reductase ◽  
Epoxide Reductase ◽  
Kinetics Of

Vitamin K epoxide reductase significantly improves carboxylation in a cell line overexpressing factor X

Blood ◽  
2005 ◽  
Vol 106 (12) ◽  
pp. 3811-3815 ◽  
Author(s):  
Yan-Mei Sun ◽  
Da-Yun Jin ◽  
Rodney M. Camire ◽  
Darrel W. Stafford
Keyword(s):  
Binding Site ◽  
Cell Line ◽  
Vitamin K ◽  
Turnover Rate ◽  
Factor X ◽  
Vitamin K Epoxide Reductase ◽  
Transfected Cells ◽  
Epoxide Reductase ◽  
A Cell ◽  
Practical Implications

Previously we reported that we could increase the fraction of carboxylated factor X by reducing the affinity of the propeptide for its binding site on human gamma glutamyl carboxylase. We attributed this to an increased turnover rate. However, even with the reduced affinity propeptide, when sufficient overproduction of factor X is achieved, there is still a significant fraction of uncarboxylated recombinant factor X. We report here that the factor X of such a cell line was only 52% carboxylated but that the fraction of carboxylated factor X could be increased to 92% by coexpressing the recently identified gene for vitamin K epoxide reductase. Because vitamin K is in excess in both the untransfected and vitamin K epoxide reductase (VKOR)–transfected cells, the simplest explanation for this result is that VKOR catalyzes both the reduction of vitamin K epoxide to vitamin K and the conversion of vitamin K to vitamin K hydroquinone. In addition to its mechanistic relevance, this observation has practical implications for overproducing recombinant vitamin K–dependent proteins for therapeutic use.

Identification of the gene for vitamin K epoxide reductase

Nature ◽  
2004 ◽  
Vol 427 (6974) ◽  
pp. 541-544 ◽  
Author(s):  
Tao Li ◽  
Chun-Yun Chang ◽  
Da-Yun Jin ◽  
Pen-Jen Lin ◽  
Anastasia Khvorova ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Epoxide Reductase ◽  
Epoxide Reductase

scholarly journals Identification of new superwarfarin-type rodenticides by structural similarity. The docking of ligands on the vitamin K epoxide reductase enzyme’s active site

2015 ◽  
Vol 7 (1) ◽  
pp. 108-122
Author(s):  
László Ferencz ◽  
Daniela Lucia Muntean
Keyword(s):  
Vitamin K ◽  
Chemical Structure ◽  
Enzyme Inhibitors ◽  
Structural Similarity ◽  
Vitamin K Epoxide Reductase ◽  
Pubchem Compound ◽  
Structure Search ◽  
Epoxide Reductase ◽  
Compound Database ◽  
Similarity Thresholds

Abstract The rodenticide brodifacoum is highly toxic to mammals and birds, and extremely toxic to fish. It is a highly cumulative poison due to its high lipophilicity and extremely slow elimination. For this reason, it may be interesting to find similar compounds in order to enlarge the spectrum of vitamin K epoxide reductase enzyme inhibitors used today in pest control. We used the Similar Compounds search type of the Chemical Structure Search of the PubChem Compound Database to locate records that are similar to the chemical structure of brodifacoum, using pre-specified similarity thresholds. Using the threshold ≥ than 95% for the similar structures criteria, we found 14 compounds (from over 30 million entries) that meet this criteria. Two of these compounds have a better binding affinity to vitamin K epoxide reductase enzyme than brodifacoum, but the binding energy of the other 12 substances is also high, having identical or lower lipophilicity; consequently, they will eliminate faster, possibly lacking a part of the adverse effects.

scholarly journals Warfarin and vitamin K epoxide reductase: a molecular accounting for observed inhibition

Blood ◽  
2018 ◽  
Vol 132 (6) ◽  
pp. 647-657 ◽  
Author(s):  
Sangwook Wu ◽  
Xuejie Chen ◽  
Da-Yun Jin ◽  
Darrel W. Stafford ◽  
Lee G. Pedersen ◽  
...  
Keyword(s):  
Vitamin K ◽  
Md Simulation ◽  
Functional Study ◽  
Binding Motif ◽  
Vitamin K Epoxide Reductase ◽  
Stacking Interaction ◽  
Key Points ◽  
Epoxide Reductase

Key Points Warfarin reversibly inhibits VKOR by forming a T-shaped stacking interaction with residue Y139 of the proposed TYA warfarin-binding motif. Warfarin-resistant nonbleeding phenotype for patients bearing VKOR mutations explained by MD simulation and cell-based functional study.

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