The vitamin K-dependent carboxylase.

@article{Presnell2002TheVK,
  title={The vitamin K-dependent carboxylase.},
  author={Steven R. Presnell and Darrel W Stafford},
  journal={Thrombosis and haemostasis},
  year={2002},
  volume={87 6},
  pages={
          937-46
        }
}
The only known biological function of Vitamin K (Fig. 1) in animals is as a required cofactor for the production of the unusual amino acid, -carboxyglutamate (Gla). This amino acid has a profound role in human blood coagulation. Several blood proteins require the presence of nine to thirteen Gla residues for normal function; these are the socalled Vitamin K-dependent (VKD) proteins. While some of the VKD blood proteins have a pro-coagulant function (prothrombin, and factors VII, IX, and X… 

Figures from this paper

Vitamin K-dependent gamma-glutamylcarboxylation: an ancient posttranslational modification.

Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle.

Sequence based search methods reveal that human VKORC1 belongs to a large family of homologous genes found in vertebrates, insects, plants, protists, archea, and bacteria, and all orthologs share five completely conserved amino acids, including two cysteines found in a tetrapeptide motif presumably required for redox function.

Structure and function of vitamin K epoxide reductase.

Binding of the Factor IX γ-Carboxyglutamic Acid Domain to the Vitamin K-dependent γ-Glutamyl Carboxylase Active Site Induces an Allosteric Effect That May Ensure Processive Carboxylation and Regulate the Release of Carboxylated Product*

The similarity between the steady state carboxylation rate constant and product Dissociation rate constant suggests that product release is rate-limiting and the increased dissociation rate after carboxyglutamic acid contributes to the release of product.

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

It is reported that the factor X of such a cell line was only 52% carboxylated but that the fraction of car boxylated factor X could be increased to 92% by coexpressing the recently identified gene for vitamin K epoxide reductase, and the simplest explanation for this result is that VKOR catalyzes both the reduction of vitaminK epoxide to vitamin K and the conversion of vitamin K to vitaminK hydroquinone.

Functional study of the vitamin K cycle in mammalian cells.

The results suggest that the cell system is a good model for studying the vitamin K cycle, the warfarin-resistant enzyme reducing vitamin K to hydroquinone (KH₂) is probably not NQO1, there appears to be a warFarin-sensitive enzyme other than VKOR that reduces vitaminK to KH⁂, and the primary function of VKOR is the reduction of KO to vitamin K.

A new model for vitamin K-dependent carboxylation: the catalytic base that deprotonates vitamin K hydroquinone is not Cys but an activated amine.

  • M. RishavyB. Pudota K. Berkner
  • Chemistry, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2004
The identity of the catalytic base is critical to understanding carboxylase mechanism and this work will therefore impact both reinterpretation of previous studies and future ones that define how this important enzyme functions.

Membrane Topology Mapping of Vitamin K Epoxide Reductase by in Vitro Translation/Cotranslocation*

The experimentally derived membrane topology of VKOR is suggested to be a type III membrane protein with three transmembrane domains, which agrees well with the prediction by the topology prediction program TMHMM.

Unique secretion mode of human protein Z: its Gla domain is responsible for inefficient, vitamin K-dependent and warfarin-sensitive secretion.

It was concluded that the difference observed in secretion patterns of protein Z and factor X was mainly based on the structure of their gamma-carboxyglutamic acid domains.
...

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