Carboxyglutamic acid

Hydroxylated amino acids (eg, 4-hydroxyproline, 5-hydroxylysine) and A/-methylated amino acids (eg, /V-methylhistidine) are obtained by the acid hydrolysis of proteins. y-Carboxyglutamic acid occurs as a component of some sections of protein molecules it decarboxylates spontaneously to L-glutamate at low pH. These examples are formed upon the nontranslational modification of protein and are often called secondary protein amino acids... 

Aminoadipic acid y-Carboxyglutamic acid Pyroglutatnic acid Phosphoserine Phospho threonine Phospho tyrosine... 

Furie, B., Bouchard, B.A. andFurie, B.C. (1999) Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid. Blood, 93 (6), 1798-1808. 

Kelleher, N.L., Zubarev, R.A., Bush, K., Eurie, B., Eurie, B.C., McLafferty, E.W. and Walsh, C.T. (1999) Localization of labile posttranslational modifications by electron capture dissociation the case of gamma-carboxyglutamic acid. Analytical Chemistry, 71, 4250-4253. 

C2 domains, 46 460-465 y-carboxyglutamic acid sites, 46 465 70 Calcium nitrate, preparation of, 6 125 Calcium pentaphosphate, 4 37-38 Calcium phthalocyanine, preparation of, 7 ... 

Coumarins are competitive inhibitors of vitamin K, which is required for the formation in the liver of the amino acid, gamma-carboxyglutamic acid. This is necessary for the synthesis of prothrombin and factors VII, IX and X (Figure 17.1). After starting treatment the anticoagulant effect is delayed until the concentration of normal coagulation factors falls (36-72 h). The effects can be reversed by vitamin K (slow maximum effect only after 3-6 h) or by whole blood or plasma (fast). Gut bacteria synthesise vitamin K and thus are an important source of this vitamin. Consequently, antibiotics can cause excessive prolongation of the prothrombin time in patients otherwise adequately controlled on warfarin. 

It is also important to note that the coagulation mechanism in vivo does not occur in solution, but is localized to activated cell surfaces expressing anionic phospholipids such as phosphatidylserine, and is mediated by Ca2+ bridging between the anionic phospholipids and 7-carboxyglutamic acid residues of the clotting factors. This is the basis for using calcium chelators such as ethylenediamine tetraacetic acid (EDTA) or citrate to prevent blood from clotting in a test tube. 

Price, P. A., Otsuka, A. S., Poser, J. W. Comparison of 7-carboxyglutamic acid-containing proteins from bovine and swordfish bone Primary structure and Ca++ binding, In calcium binding protein and calcium function, p.333. Wassermann, R. A., Corradino, E., Carafoli,... 

King, Jr., K. 7-Carboxyglutamic acid in fossil bones and its significance for amino acid dating. Nature 273, 41 (1978)... 

Czerwiec E, Kalume DE, Roepstorff P, Hambe B, Furie B, Furie BC, Stenflo J (2006) Novel y-Carboxyglutamic Acid-Containing Peptides from the Venom of Conus textile. FEBS J 273 2779... 

N. L. Kelleher, R. A. Zubarev, K. Bush, B. Furie, B. C. Furie, F. W. McLafferty, and C. T. Walsh, Localization of labile posttranslational modifications by electron capture dissociation The case of y-carboxyglutamic acid, Anal. Chem., 71 (1999) 4250 1253. 

SpA, Staphylococcal protein A PpL, protein L from Peptostreptococcus Magnus IgG, immunoglobulin G Gla, y-carboxyglutamic acid SPR, surface plasmon resonance ELISA, enzyme-linked immunosorbent assay FITC, fluorescein isothiocyanate NMR, nuclear magnetic resonance... 

The majority of conotoxin structures (115 of 125 structures in the PDB) have been determined by NMR spectroscopy as opposed to X-ray crystallography. They have significant structural diversity as a result of their diverse sequences and disulphide connectivities. Furthermore, conotoxins also have a large number of post-translational modifications, including the presence of hydroxyproline, y-carboxyglutamic acid and bromotryptophan residues, epimerisation, glycosyla-tion and amidation,144,145 that enhance their structural diversity. A recent analysis of NMR data for the unusual amino acids present in conotoxins3 provides a reference source for chemical shifts of post-translationally modified amino acids. 

Processed carboxyl terminal. O = hydroxyproline residue. Z = 7-carboxyglutamic acid residue. 

Widespread e.g. Vaccinium corymbosum (Ericaceae), Medicago saliva (alfalfa) (Fabaceae), Castaneasp. (chestnut) (Fagaceae) [leaf]), Triticum aestivum (Poaceae) Dihydro form (KH ) coenzyme for "y-carboxyglutamic acid formation on procoagulant factors II, VII, IX X, anticoagulant proteins C S, matrix Gla protein osteocalcin... 

Intestinal bacteria dihydro form (KH9) coenzyme for "y-carboxyglutamic acid formation on procagulant factors II, VII, IX X, anticoagulant proteins C S, matrix Gla protein osteocalcin... 

The Mannich bases investigated are acctoacetic and malonic acid derivatives, Y-carboxyglutamic acid included. - Compounds having the lactone structure give preferably decarboxylation of the ester groups not involved in the lactone ring. - ... 

Boggs, N. T., Chemical modification of peptides containing y-carboxyglutamic acid, J. Org. Chem., 47, 1812. 1982. 

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