Structural and mechanistic investigations on CC bond forming α-oxoamine synthase allowing L-glutamate as substrate

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 identifi...

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Bibliographic Details
Published in:International journal of biological macromolecules 2024-05, Vol.268 (Pt 1), p.131696-131696, Article 131696
Main Authors: Zhang, Dai-Ke, Song, Kai-Yuan, Yan, Ya-Qian, Zheng, Jian-Ting, Xu, Jun, Da, Lin-Tai, Xu, Min-Juan
Format: Article
Language:English
Subjects:
Amino transformation
Bacterial Proteins - chemistry
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Catalytic Domain
Crystallography, X-Ray
Glutamic Acid - chemistry
Models, Molecular
Protein Conformation
Pyridoxal 5′-phosphate-dependent enzyme
Pyridoxal Phosphate - chemistry
Pyridoxal Phosphate - metabolism
Streptomyces - enzymology
Structure-Activity Relationship
Substrate Specificity
α-Oxoamine synthase
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Summary: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.
ISSN:0141-8130
1879-0003
DOI:10.1016/j.ijbiomac.2024.131696