Gamma-glutamyl carboxylase is an enzyme that in humans is encoded by the GGCX gene, located on chromosome 2 at 2p12.[4]
GGCX | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | GGCX, VKCFD1, gamma-glutamyl carboxylase, Gamma-glutamyl carboxylase; GGCX | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 137167 MGI: 1927655 HomoloGene: 639 GeneCards: GGCX | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Gamma-glutamyl carboxylase is an enzyme that catalyzes the posttranslational modification of vitamin K-dependent proteins. Many of these vitamin K-dependent proteins are involved in coagulation so the function of the encoded enzyme is essential for hemostasis.[5] Most gla domain-containing proteins depend on this carboxylation reaction for posttranslational modification.[6] In humans, the gamma-glutamyl carboxylase enzyme is most highly expressed in the liver.
Gamma-glutamyl carboxylase oxidizes Vitamin K hydroquinone to Vitamin K 2,3 epoxide, while simultaneously adding CO2 to protein-bound glutamic acid (abbreviation = Glu) to form gamma-carboxyglutamic acid (also called gamma-carboxyglutamate, abbreviation = Gla). Presence of two carboxylate groups causes chelation of Ca2+ , resulting in change in tertiary structure of protein and its activation. The carboxylation reaction will only proceed if the carboxylase enzyme is able to oxidize vitamin K hydroquinone to vitamin K epoxide at the same time; the carboxylation and epoxidation reactions are said to be coupled reactions.[7][8]
No experimental structure is known for GGCX, limiting understanding of its reaction mechanism. Based on the fact that the two reactions are coupled, a computational study is able to propose how the reactants interact with each other to form the products.[9] Lys228 has been shown to be the residue responsible for starting the reaction.[10] How the enzyme holds the reactants in place to have them interact with each other remains poorly shown. 491-507 and 395-401 are probably responsible for propeptide and glutamate binding respectively.[11]
Mutations in this gene are associated with vitamin K-dependent coagulation defect and PXE-like disorder with multiple coagulation factor deficiency.[5][12]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.