The vitamin K-dependent carboxylase.

  title={The vitamin K-dependent carboxylase.},
  author={Steven R. Presnell and Darrel W Stafford},
  journal={Thrombosis and haemostasis},
  volume={87 6},
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… 

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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.



Mechanism of action of vitamin K: synthesis of gamma-carboxyglutamic acid.

  • J. Suttie
  • Biology, Chemistry
    CRC critical reviews in biochemistry
  • 1980
Vitamin K (2-methyl-3-phytyl-1,4-naphthoquinone) is required for the synthesis of prothrombin, Factor VII, Factor IX, Factor X, and a number of newly discovered proteins. These plasma proteins

Mechanism Of Action Of Vitamin K: Synthesis Of Y-Carboxyglutamic Aci

Vitamin K (2-methyl-3-phytyl-1,4-naphthoquinone) is required for the synthesis of prothrombin, Factor VII, Factor IX, Factor X, and a number of newly discovered proteins. These plasma proteins

The vitamin K-dependent carboxylation reaction

  • C. Vermeer
  • Biology
    Molecular and Cellular Biochemistry
  • 2004
It seems that (like for instance the glycosylation) the vitamin K-dependent carboxylation is a normal post-translational modification, which is required for the correct function of a certain class of Ca2+-binding proteins.

Vitamin K-dependent carboxylase: influence of the "propeptide" region on enzyme activity.

The Propeptides of the Vitamin K-dependent Proteins Possess Different Affinities for the Vitamin K-dependent Carboxylase*

It is demonstrated that the affinities of the propeptides of the vitamin K-dependent proteins vary over a considerable range; this may have important physiological consequences in the levels of vitamin K -dependent proteins and the biochemical mechanism by which these substrates are modified by the carboxylase.

Vitamin K-dependent carboxylase. Solubilization and properties.

Observations suggest that the energy required to drive the carboxylation reaction is derived from the oxidation of the reduced form of vitamin K.

Identification and purification to near homogeneity of the vitamin K-dependent carboxylase.

The bovine vitamin K-dependent carboxylase is identified and purified it to near homogeneity by an affinity procedure that uses the 59-amino acid peptide FIXQ/S.

Synthesis of vitamin K‐dependent proteins

  • J. Suttie
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1993
The primary gene product of the vitamin K‐dependent proteins contains a homologous propeptide extension between the amino terminus of the mature protein and signal peptide that serves to dock the protein substrate to the enzyme catalyzing the carboxylation event, and to also alter the apparent Km of the Glu binding site of the enzyme.