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Conantokin-G Precursor and Its Role in Gamma-Carboxylation by a Vitamin K-dependent Carboxylase From a Conus Snail

Conantokin-G Precursor and Its Role in Gamma-Carboxylation by a Vitamin K-dependent Carboxylase From a Conus Snail

P K Bandyopadhyay, C J Colledge, C S Walker, L M Zhou, D R Hillyard, B M Olivera

J Biol Chem. 1998 Mar 6;273(10):5447-50.

PMID: 9488665

Abstract:

Conantokin-G isolated from the marine snail Conus geographus is a 17-amino acid gamma-carboxyglutamate (Gla)-containing peptide that inhibits the N-methyl-D-aspartate receptor. We describe the cloning and sequence of conantokin-G cDNA and the possible role of the propeptide sequence. The cDNA encodes a 100amino acid peptide. The N-terminal 80 amino acids constitute the prepro-sequence, and the mature peptide is derived from the remaining C-terminal residues after proteolysis, C-terminal amidation, and a unique post-translational modification, gamma-carboxylation of glutamate residues to Gla. Mature conantokin-G peptide containing Glu residues (E.Con-G) in place of Gla is a poor substrate for the vitamin K-dependent gamma-glutamyl carboxylase (apparent Km = 3.4 mM). Using peptides corresponding to different segments of the propeptide we investigated a potential role for the propeptide sequences in gamma-carboxylation. Propeptide segment -20 to -1 covalently linked to E.Con-G or the synthetic pentapeptide FLEEL increased their apparent affinities 2 orders of magnitude. These substrates are not efficiently carboxylated by the bovine microsomal gamma-glutamyl carboxylase, suggesting differences in specificities between the Conus and the mammalian enzyme. However, the role of propeptide in enhancing the efficiency of carboxylation is maintained.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP93438654	Conantokin G		93438-65-4	Price

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