Crystal structure of BtrK, a decarboxylase involved in the (S)-4-amino-2-hydroxybutyrate (AHBA) formation during butirosin biosynthesis

Autor: Laura A. Rivas Arenas, Fernanda C.R. de Paiva, Nicolas de O． Rossini, YanYan Li, Jonathan Spencer, Peter Leadlay, Marcio V.B. Dias
Rok vydání: 2022
Předmět:
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 0022-2860
DOI: 10.1016/j.molstruc.2022.133576
Popis: Butirosin is an aminoglycoside that has an (S)-4-amino-2-hydroxybutyrate (AHBA) moiety capable of preventing the attack of several aminoglycoside modifying enzymes. The biosynthesis and the attachment of the AHBA to the 2-deoxystreptamine (2-DOS) involve seven enzymes that use glutamate as a precursor. BtrK is a pyridoxal-5-phosphate (PLP)-dependent enzyme and performs the decarboxylation of a glutamyl moiety tethered to the peptidyl carrier protein BtrI during the AHBA biosynthetic pathway. The structure of BtrK was solved at 1.4 Å resolution and indicated a conserved folding. The PLP is covalently linked through a Schiff base to Lys49 and performs intensive hydrogen bond interactions with active site residues that are also conserved in other members of type IV PLP-dependent enzymes. Additionally, a docking simulation indicates the possible anchoring of a substrate fragment constituted of O-S-γ-Lglutamylpantetheine-4′-phosphate. The glutamyl moiety forms a number of hydrogen bonds with the putative active site residues of BtrK. The pantetheine moiety seems to perform only a few interactions and should adopt a more flexible conformation. The description of BtrK structure contributes to the understanding of the large family of PLP-dependent enzymes and also in this crucial step during the butirosin biosynthesis.\ud \ud
Databáze: OpenAIRE
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