Polypeptide chains containing D-gamma-hydroxyvaline.
Polypeptide chains containing D-gamma-hydroxyvaline.
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DOI：
10.1021/ja050088m
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发表时间：
2005-04
影响因子：
15
通讯作者：
Katarzyna Pisarewicz;D. Mora;F. Pflueger;G. Fields;F. Marí
中科院分区：
文献类型：
--
作者：
Katarzyna Pisarewicz;D. Mora;F. Pflueger;G. Fields;F. Marí
生命具有无法解释的独特的l-同手性。蛋白质通常仅将l-氨基酸并入其序列中。在本研究中，d-缬氨酸和d-γ-羟基缬氨酸（d-Hyv; V）已被发现在核糖体表达的多肽链。从剑尾鱼（Conus gladiator）毒液中分离得到4个肽段，分别为gld-V/gld-V '和mus-V/mus-V'，用nano/pico-NMR和MS/MS方法测定了它们的全序列（gld-V/gld-V' = Ala-Hyp-Ala-Asn-Ser-d-Hyv-Trp-Ser和mus-V/mus-V' = Ser-Hyp-Ala-Asn-Ser-d-Hyv-Trp-Ser）。含有γ-羟基化残基的氨基酸三联体Ser-d-Hyv-Trp是一种新的结构基序，其通过d-氨基酸与其相邻的l-对应物之间的特异性相互作用而稳定。这些相互作用抑制内酯化，这是一种通常由γ-羟基化残基引发的肽骨架断裂过程。具有Ser-d-Hyv-Trp基序的芋螺肽被称为γ-羟基芋螺烷。我们还分离出类似的conopeptides（gld-V和mus-V）含有d-Val而不是d-Hyv，这些被称为conophans。γ-羟基芋螺烷和芋螺烷是特别非典型的，因为（i）它们不像大多数芋螺肽那样受到限制，（ii）它们的长度极短，（iii）它们具有高含量的羟基化残基，和（iv）它们的序列与序列数据库中的其它肽没有紧密匹配。它们的修饰似乎是锥螺毒液中发现的一种新的超羟基化机制的一部分，该机制增强了神经元靶向作用。在该肽家族中发现d-Val和d-Hyv表明存在能够氧化d-Val的相应d-立体特异性酶。
Life has an unexplained and distinct l-homochirality. Proteins typically incorporate only l-amino acids into their sequences. In the present study, d-Val and d-gamma-hydroxyvaline (d-Hyv; V) have been found within 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 complete sequences (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 amino acid triad that contains the gamma-hydroxylated residue, Ser-d-Hyv-Trp, is a novel structural motif that is stabilized by specific interactions between the d-amino acid and its neighboring l-counterparts. These interactions inhibit lactonization, a peptide backbone scission process that would normally be initiated by gamma-hydroxylated residues. Conopeptides possessing the Ser-d-Hyv-Trp motif have been termed gamma-hydroxyconophans. We have also isolated analogous conopeptides (gld-V and mus-V) containing d-Val instead of d-Hyv; these are termed conophans. gamma-Hydroxyconophans and conophans are particularly atypical because (i) they are not constrained as most conopeptides, (ii) they are extremely short in length, (iii) they have a high content of hydroxylated residues, and (iv) their sequences have no close match with other peptides in sequence databases. Their modifications appear to be part of a novel hyperhydroxylation mechanism found within the venom of cone snails that enhances neuronal targeting. The finding of d-Val and d-Hyv within this family of peptides suggests the existence of a corresponding d-stereospecific enzyme capable of d-Val oxidation.