| Structural highlights
Function
[CLPS_STRNR] Involved in the biosynthesis of albonoursin (cyclo[(alpha,beta-dehydro-Phe)-(alpha,beta-dehydro-Leu)]), an antibacterial peptide. It uses activated amino acids in the form of aminoacyl-tRNAs (aa-tRNAs) as substrates to catalyze the ATP-independent formation of cyclodipeptides which are intermediates in diketopiperazine (DKP) biosynthetic pathways. Catalyzes the formation of cyclo(L-Phe-L-Leu) (cFL) as major products from L-L-phenylalanyl-tRNA(Phe) and L-leucyl-tRNA(Leu). AlbC can also incorporate various nonpolar residues, such as L-phenylalanine, L-leucine, L-tyrosine and L-methionine, and to a much lesser extent L-alanine and L-valine, into cyclodipeptides. Indeed, ten possible cyclodipeptides composed of L-phenylalanine, L-leucine, L-tyrosine and L-methionine are all synthesized to detectable amounts by AlbC.[1] [2]
Publication Abstract from PubMed
Cyclodipeptide synthases (CDPSs) belong to a newly defined family of enzymes that use aminoacyl-tRNAs (aa-tRNAs) as substrates to synthesize the two peptide bonds of various cyclodipeptides, which are the precursors of many natural products with noteworthy biological activities. Here, we describe the crystal structure of AlbC, a CDPS from Streptomyces noursei. The AlbC structure consists of a monomer containing a Rossmann-fold domain. Strikingly, it is highly similar to the catalytic domain of class-I aminoacyl-tRNA synthetases (aaRSs), especially class-Ic TyrRSs and TrpRSs. AlbC contains a deep pocket, highly conserved among CDPSs. Site-directed mutagenesis studies indicate that this pocket accommodates the aminoacyl moiety of the aa-tRNA substrate in a way similar to that used by TyrRSs to recognize their tyrosine substrates. These studies also suggest that the tRNA moiety of the aa-tRNA interacts with AlbC via at least one patch of basic residues, which is conserved among CDPSs but not present in class-Ic aaRSs. AlbC catalyses its two-substrate reaction via a ping-pong mechanism with a covalent intermediate in which l-Phe is shown to be transferred from Phe-tRNA(Phe) to an active serine. These findings provide insight into the molecular bases of the interactions between CDPSs and their aa-tRNAs substrates, and the catalytic mechanism used by CDPSs to achieve the non-ribosomal synthesis of cyclodipeptides.
Cyclodipeptide synthases, a family of class-I aminoacyl-tRNA synthetase-like enzymes involved in non-ribosomal peptide synthesis.,Sauguet L, Moutiez M, Li Y, Belin P, Seguin J, Le Du MH, Thai R, Masson C, Fonvielle M, Pernodet JL, Charbonnier JB, Gondry M Nucleic Acids Res. 2011 May 1;39(10):4475-89. Epub 2011 Feb 3. PMID:21296757[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lautru S, Gondry M, Genet R, Pernodet JL. The albonoursin gene Cluster of S noursei biosynthesis of diketopiperazine metabolites independent of nonribosomal peptide synthetases. Chem Biol. 2002 Dec;9(12):1355-64. PMID:12498889
- ↑ Gondry M, Sauguet L, Belin P, Thai R, Amouroux R, Tellier C, Tuphile K, Jacquet M, Braud S, Courcon M, Masson C, Dubois S, Lautru S, Lecoq A, Hashimoto S, Genet R, Pernodet JL. Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes. Nat Chem Biol. 2009 Jun;5(6):414-20. doi: 10.1038/nchembio.175. PMID:19430487 doi:http://dx.doi.org/10.1038/nchembio.175
- ↑ Sauguet L, Moutiez M, Li Y, Belin P, Seguin J, Le Du MH, Thai R, Masson C, Fonvielle M, Pernodet JL, Charbonnier JB, Gondry M. Cyclodipeptide synthases, a family of class-I aminoacyl-tRNA synthetase-like enzymes involved in non-ribosomal peptide synthesis. Nucleic Acids Res. 2011 May 1;39(10):4475-89. Epub 2011 Feb 3. PMID:21296757 doi:10.1093/nar/gkr027
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