Polypeptide Chains Containing D--Hydroxyvaline
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- 作者：Katarzyna Pisarewicz ; David Mora ; Fred C. Pflueger ; Gregg B. Fields ; and Frank Marí
- 刊名：Journal of the American Chemical Society
- 出版年：2005
- 出版时间：May 4, 2005
- 年：2005
- 卷：127
- 期：17
- 页码：6207 - 6215
- 全文大小：270K
- 年卷期：v.127,no.17(May 4, 2005)
- ISSN：1520-5126
文摘
Life has an unexplained and distinct L-homochirality. Proteins typically incorporate only L-aminoacids into their sequences. In the present study, D-Val and D-
-hydroxyvaline (D-Hyv; V*) have been foundwithin ribosomally expressed polypeptide chains. Four conopeptides were initially isolated, gld-V*/gld-V*'from the venom of Conus gladiator and mus-V*/mus-V*' from the venom of Conus mus. Their completesequences (gld-V*/gld-V*' = Ala-Hyp-Ala-Asn-Ser-D-Hyv-Trp-Ser and mus-V*/mus-V*' = Ser-Hyp-Ala-Asn-Ser-D-Hyv-Trp-Ser) were determined by a combination of nano/pico-NMR and MS/MS methods. The aminoacid triad that contains the -hydroxylated residue, Ser-D-Hyv-Trp, is a novel structural motif that is stabilizedby specific interactions between the D-amino acid and its neighboring L-counterparts. These interactionsinhibit lactonization, a peptide backbone scission process that would normally be initiated by -hydroxylatedresidues. Conopeptides possessing the Ser-D-Hyv-Trp motif have been termed -hydroxyconophans. Wehave also isolated analogous conopeptides (gld-V and mus-V) containing D-Val instead of D-Hyv; theseare termed conophans. -Hydroxyconophans and conophans are particularly atypical because (i) they arenot constrained as most conopeptides, (ii) they are extremely short in length, (iii) they have a high contentof hydroxylated residues, and (iv) their sequences have no close match with other peptides in sequencedatabases. Their modifications appear to be part of a novel hyperhydroxylation mechanism found withinthe venom of cone snails that enhances neuronal targeting. The finding of D-Val and D-Hyv within thisfamily of peptides suggests the existence of a corresponding D-stereospecific enzyme capable of D-Valoxidation.
-hydroxyvaline (D-Hyv; V*) have been foundwithin ribosomally expressed polypeptide chains. Four conopeptides were initially isolated, gld-V*/gld-V*'from the venom of Conus gladiator and mus-V*/mus-V*' from the venom of Conus mus. Their completesequences (gld-V*/gld-V*' = Ala-Hyp-Ala-Asn-Ser-D-Hyv-Trp-Ser and mus-V*/mus-V*' = Ser-Hyp-Ala-Asn-Ser-D-Hyv-Trp-Ser) were determined by a combination of nano/pico-NMR and MS/MS methods. The aminoacid triad that contains the -hydroxylated residue, Ser-D-Hyv-Trp, is a novel structural motif that is stabilizedby specific interactions between the D-amino acid and its neighboring L-counterparts. These interactionsinhibit lactonization, a peptide backbone scission process that would normally be initiated by -hydroxylatedresidues. Conopeptides possessing the Ser-D-Hyv-Trp motif have been termed -hydroxyconophans. Wehave also isolated analogous conopeptides (gld-V and mus-V) containing D-Val instead of D-Hyv; theseare termed conophans. -Hydroxyconophans and conophans are particularly atypical because (i) they arenot constrained as most conopeptides, (ii) they are extremely short in length, (iii) they have a high contentof hydroxylated residues, and (iv) their sequences have no close match with other peptides in sequencedatabases. Their modifications appear to be part of a novel hyperhydroxylation mechanism found withinthe venom of cone snails that enhances neuronal targeting. The finding of D-Val and D-Hyv within thisfamily of peptides suggests the existence of a corresponding D-stereospecific enzyme capable of D-Valoxidation.