3WV5

Complex structure of VinN with 3-methylaspartate

Summary for 3WV5

• Entry DOI: 10.2210/pdb3wv5/pdb
• Related: 3WV4
• Descriptor: Non-ribosomal peptide synthetase, (2S,3S)-3-methyl-aspartic acid (3 entities in total)
• Functional Keywords: five-layered alpha-beta-alpha-beta-alpha sandwich fold, ligase, atp binding
• Biological source: Streptomyces halstedii
• Total number of polymer chains: 2
• Total formula weight: 96643.36

Authors

Miyanaga, A.,Cieslak, J.,Shinohara, Y.,Kudo, F.,Eguchi, T. (deposition date: 2014-05-15, release date: 2014-10-01, Last modification date: 2023-11-08)

Primary citation

Miyanaga, A.,Cieslak, J.,Shinohara, Y.,Kudo, F.,Eguchi, T.
The crystal structure of the adenylation enzyme VinN reveals a unique beta-amino acid recognition mechanism
J.Biol.Chem., 289:31448-31457, 2014

PubMed Abstract: Adenylation enzymes play important roles in the biosynthesis and degradation of primary and secondary metabolites. Mechanistic insights into the recognition of α-amino acid substrates have been obtained for α-amino acid adenylation enzymes. The Asp residue is invariant and is essential for the stabilization of the α-amino group of the substrate. In contrast, the β-amino acid recognition mechanism of adenylation enzymes is still unclear despite the importance of β-amino acid activation for the biosynthesis of various natural products. Herein, we report the crystal structure of the stand-alone adenylation enzyme VinN, which specifically activates (2S,3S)-3-methylaspartate (3-MeAsp) in vicenistatin biosynthesis. VinN has an overall structure similar to that of other adenylation enzymes. The structure of the complex with 3-MeAsp revealed that a conserved Asp(230) residue is used in the recognition of the β-amino group of 3-MeAsp similar to α-amino acid adenylation enzymes. A mutational analysis and structural comparison with α-amino acid adenylation enzymes showed that the substrate-binding pocket of VinN has a unique architecture to accommodate 3-MeAsp as a β-amino acid substrate. Thus, the VinN structure allows the first visualization of the interaction of an adenylation enzyme with a β-amino acid and provides new mechanistic insights into the selective recognition of β-amino acids in this family of enzymes.

PubMed: 25246523
DOI: 10.1074/jbc.M114.602326

Experimental method

X-RAY DIFFRACTION (2.2 Å)