3OQV

AlbC, a cyclodipeptide synthase from Streptomyces noursei

Summary for 3OQV

• Entry DOI: 10.2210/pdb3oqv/pdb
• Descriptor: AlbC, DITHIANE DIOL, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: rossmann fold, cyclodipeptide synthase, aminoacyl-trna, protein binding
• Biological source: Streptomyces noursei
• Total number of polymer chains: 1
• Total formula weight: 28248.39

Authors

Sauguet, L.,Ledu, M.H.,Charbonnier, J.B.,Gondry, M. (deposition date: 2010-09-04, release date: 2011-02-16, Last modification date: 2024-02-21)

Primary citation

Sauguet, L.,Moutiez, M.,Li, Y.,Belin, P.,Seguin, J.,Le Du, M.H.,Thai, R.,Masson, C.,Fonvielle, M.,Pernodet, J.L.,Charbonnier, J.B.,Gondry, M.
Cyclodipeptide synthases, a family of class-I aminoacyl-tRNA synthetase-like enzymes involved in non-ribosomal peptide synthesis.
Nucleic Acids Res., 39:4475-4489, 2011

PubMed Abstract: 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.

PubMed: 21296757
DOI: 10.1093/nar/gkr027

Experimental method

X-RAY DIFFRACTION (1.9 Å)