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.
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http://purl.uniprot.org/cit... | rdfs:comment | 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. | lld:uniprot |
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http://purl.uniprot.org/cit... | skos:exactMatch | http://purl.uniprot.org/pub... | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:name | J. Biol. Chem. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:author | Hillyard D.R. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:author | Olivera B.M. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:author | Colledge C.J. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:author | Bandyopadhyay P.K. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:author | Walker C.S. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:author | Zhou L.-M. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:date | 1998 | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:pages | 5447-5450 | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:title | Conantokin-G precursor and its role in gamma-carboxylation by a vitamin K-dependent carboxylase from a Conus snail. | lld:uniprot |
http://purl.uniprot.org/cit... | uniprot:volume | 273 | lld:uniprot |
http://purl.uniprot.org/cit... | dc-term:identifier | doi:10.1074/jbc.273.10.5447 | lld:uniprot |
uniprot-protein:P07231 | uniprot:citation | http://purl.uniprot.org/cit... | lld:uniprot |
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