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

Autor(es)

Rivas Arenas, Laura A. ; de Paiva, Fernanda C. R. ; Rossini, Nicolas de O. ; Li, YanYan ; Spencer, Jonathan ; Leadlay, Peter ; Dias, Marcio V. B.

• Tipo de documento: Artigo Científico
• Fonte: Journal of Molecular Structure; v. 1267, p. 10-pg., 2022-06-30.

Resumo

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 A 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-gamma-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. (C) 2022 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 18/00351-1 - Biologia Estrutural aplicada às enzimas envolvidas na biossíntese de produtos naturais: aplicações biotecnológicas e entendimento molecular de reações enzimáticas pouco usuais
• Beneficiário: Marcio Vinicius Bertacine Dias
• Modalidade de apoio: Auxílio à Pesquisa - Regular