8XHA

Crystal structure of alpha-Oxoamine Synthase Alb29 with PLP cofactor and L-glutamate

Summary for 8XHA

• Entry DOI: 10.2210/pdb8xha/pdb
• Descriptor: 8-amino-7-oxononanoate synthase, N-({3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]pyridin-4-yl}methyl)-L-glutamic acid, PYRIDOXAL-5'-PHOSPHATE, ... (4 entities in total)
• Functional Keywords: complex, plp, l-glutamate, dimer, alpha-oxoamine synthase, transferase
• Biological source: Streptomyces albogriseolus 1-36
• Total number of polymer chains: 2
• Total formula weight: 87284.17

Authors

Xu, M.J.,Zhang, D.K. (deposition date: 2023-12-17, release date: 2024-05-01, Last modification date: 2024-05-22)

Primary citation

Zhang, D.K.,Song, K.Y.,Yan, Y.Q.,Zheng, J.T.,Xu, J.,Da, L.T.,Xu, M.J.
Structural and mechanistic investigations on CC bond forming alpha-oxoamine synthase allowing L-glutamate as substrate.
Int.J.Biol.Macromol., 268:131696-131696, 2024

PubMed Abstract: Carbon‑carbon (C-C) bonds serve as the fundamental structural backbone of organic molecules. As a critical CC bond forming enzyme, α-oxoamine synthase is responsible for the synthesis of α-amino ketones by performing the condensation reaction between amino acids and acyl-CoAs. We previously identified an α-oxoamine synthase (AOS), named as Alb29, involved in albogrisin biosynthesis in Streptomyces albogriseolus MGR072. This enzyme belongs to the α-oxoamine synthase family, a subfamily under the pyridoxal 5'-phosphate (PLP) dependent enzyme superfamily. In this study, we report the crystal structures of Alb29 bound to PLP and L-Glu, which provide the atomic-level structural insights into the substrate recognition by Alb29. We discover that Alb29 can catalyze the amino transformation from L-Gln to L-Glu, besides the condensation of L-Glu with β-methylcrotonyl coenzyme A. Subsequent structural analysis has revealed that one flexible loop in Alb29 plays an important role in both amino transformation and condensation. Based on the crystal structure of the S87G mutant in the loop region, we capture two distinct conformations of the flexible loop in the active site, compared with the wild-type Alb29. Our study offers valuable insights into the catalytic mechanism underlying substrate recognition of Alb29.

PubMed: 38642679
DOI: 10.1016/j.ijbiomac.2024.131696

Experimental method

X-RAY DIFFRACTION (2.27 Å)