Synthesis of vitamin K‐dependent proteins

@article{Suttie1993SynthesisOV,
  title={Synthesis of vitamin K‐dependent proteins},
  author={John W. Suttie},
  journal={The FASEB Journal},
  year={1993},
  volume={7},
  pages={445 - 452}
}
  • J. Suttie
  • Published 1 March 1993
  • Biology, Chemistry
  • The FASEB Journal
The unique and characteristic feature of vitamin K‐dependent proteins is the presence of 7‐carboxyglutamyl (Gla) residues formed during the post‐translational processing of these proteins. The energy needed to drive this microsomal carboxylation event comes from the reoxidation of the reduced, hydronaphthoquinone form of vitamin K to its 2,3‐epoxide. Recent studies have suggested that an intermedite epoxide alkoxide is the strong base needed to abstract a proton from the relatively unreactive… 

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

The vitamin K-dependent carboxylase.

The widespread tissue distribution of carboxylase in humans suggests the presence of additional Gla-containing proteins of diverse function, including blood proteins that contain a decreased number (or a complete absence) of Gla.

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.

Multi-site-specificity of the vitamin K-dependent carboxylase: in vitro carboxylation of des-gamma-carboxylated bone Gla protein and Des-gamma-carboxylated pro bone Gla protein.

The vitamin K-dependent carboxylase processes multiple glutamic acid residues to gamma-carboxyglutamic acid (Gla) residues in a limited number of proteins, suggesting no species or tissue variation in the enzyme specificity.

The Putative Vitamin K-dependent γ-Glutamyl Carboxylase Internal Propeptide Appears to Be the Propeptide Binding Site*

Nine mutant enzyme species were created and the results indicated that these mutations affected the propeptide binding site rather than a competitive inhibitory internal propeptid sequence.

Role of K vitamins in the regulation of tissue calcification

The only known function of vitamin K in mammals is that it serves as a cofactor for the endoplasmic enzyme gamma-glutamyl carboxylase, where it promotes the post-translational conversion of selective protein-bound glutamate residues into gamma-carboxy glutamate (Gla).

Processive Post-translational Modification

Kinetic experiments and arguments were used to show that the vitamin K-dependent carboxylase is not distributive but rather is one of the first well documented examples of an enzyme that catalyzes a processive post-translational modification.

Comparative Distribution, Metabolism, and Utilization of Phylloquinone and Menaquinone-9 in Rat Liver

  • C. K. ReedstromJ. Suttie
  • Chemistry, Biology
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
  • 1995
The relative utilization of phylloquinone and menaquinone-9 (MK-9) as substrates for the microsomal vitamin K-dependent γ-glutamyl carboxylase was determined in a rat model, and it is suggested that hepatic MK-9 is not as efficiently utilized as phyllaquinone.
...

References

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Vitamin K-dependent carboxylase. Control of enzyme activity by the "propeptide" region of factor X.

Vitamin K-dependent carboxylase. Stoichiometry of carboxylation and vitamin K 2,3-epoxide formation.

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.

Protein engineering of the propeptide of human factor IX.

Data support the current hypothesis that the propeptide contains two recognition elements: one for carboxylase recognition located towards the N-terminus, and one for propeptidase recognition Located near the C- terminus.

Vitamin K-dependent gamma-carbon-hydrogen bond cleavage and nonmandatory concurrent carboxylation of peptide-bound glutamic acid residues.

The data argue against a concerted mechanism for the cleavage of the gamma C-H bond and carboxylation and against a mechanism in which the vitamin functions solely to transfer or activate CO2.

MECHANISM of action of vitamin K.

The mechanism of action of vitamin K is discussed in terms of a new carbanion model that mimics the proton abstraction from the gamma position of protein-bound glutamate, which is the essential step leading to carboxylation and activation of the blood-clotting proteins.

Molecular cloning of matrix Gla protein: implications for substrate recognition by the vitamin K-dependent gamma-carboxylase.

The demonstration that two structures common to vitamin K-dependent proteins, the homologous propeptides domain and the invariant EXXXEXC unit, are in mature MGP indicates that des-gamma- carboxy-MGP should be an excellent in vitro gamma-carboxylase substrate for analysis of mechanisms involved in substrate recognition and product dissociation.
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