9PEP

Crystal structure of holo-pvspha

Summary for 9PEP

• Entry DOI: 10.2210/pdb9pep/pdb
• Descriptor: Aminoacyl transferase sphA (2 entities in total)
• Functional Keywords: synthase, biosynthetic protein
• Biological source: Paecilomyces variotii
• Total number of polymer chains: 6
• Total formula weight: 326170.66

Authors

Hai, Y.,He, X. (deposition date: 2025-07-02, release date: 2026-03-11)

Primary citation

Chai, W.,Luo, S.,Xi, W.,He, X.,Zhang, T.,Zou, Y.,Hai, Y.
Pyridoxal 5'-Phosphate-Dependent Enzymatic Decarboxylative Annulation.
J.Am.Chem.Soc., 2026

PubMed Abstract: Pyridoxal 5'-phosphate (PLP)-dependent enzymes are among the most versatile biocatalysts, yet transformations involving the Cγ-nucleophilic vinylglycine quinonoid (VGQ) intermediate remain exceptionally rare. Understanding the untapped reactivity of VGQ could open new avenues for developing PLP-dependent biocatalysts. Here, we establish a biocatalytic platform that artificially accesses and exploits the reactivity of this high-energy intermediate. By reprogramming SphA, a PLP-dependent enzyme that natively catalyzes decarboxylative Claisen condensation, to generate VGQ through facile decarboxylation of vinylaminomalonate, we enable a decarboxylative [3 + 2] annulation between vinylaminomalonate and electron-deficient alkenes. Crystallographic, computational, and mutagenesis studies reveal the key mechanistic features underlying this abiotic transformation. Our findings demonstrate the latent [3 + 2] annulating potential of VGQ and expand the catalytic repertoire of PLP-dependent enzymes, establishing a new strategy for the enzymatic construction of complex carbocyclic architectures.

PubMed: 41769737
DOI: 10.1021/jacs.5c20979

Experimental method

X-RAY DIFFRACTION (1.92 Å)