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Crystal structure of 3,4-dihydroxyphenylacetate 2,3-dioxygenase (DHPAO) from Acinetobacter baumannii
Structural highlights
FunctionPublication Abstract from PubMed3,4-Dihydroxyphenylacetate (DHPA) 2,3-dioxygenase (EC 1.13.11.15) from Acinetobacter baumannii (AbDHPAO) is an enzyme that catalyzes the 2,3-extradiol ring-cleavage of DHPA in the p-hydroxyphenylacetate (HPA) degradation pathway. While the biochemical reactions of various DHPAOs have been reported, only structures of DHPAO from Brevibacterium fuscum and their homologs are available. Here, we report the X-ray structure and biochemical characterization of an Fe(2+)-specific AbDHPAO that shares 12% sequence identity to the enzyme from B. fuscum. The 1.8 A X-ray structure of apo-AbDHPAO was determined with four subunits per asymmetric unit, consistent with a homotetrameric structure. Interestingly, the alphabeta-sandwiched fold of the AbDHPAO subunit is different from the dual beta-barrel-like motif of the well-characterized B. fuscum DHPAO structures; instead, it is similar to the structures of non-DHPA extradiol dioxygenases from Comamonas sp. and Sphingomonas paucimobilis. Similarly, these extradiol dioxygenases share the same chemistry owing to a conserved 2-His-1-carboxylate catalytic motif. Structure analysis and molecular docking suggested that the Fe(2+) cofactor and substrate binding sites consist of the conserved residues His12, His57, and Glu238 forming a 2-His-1-carboxylate motif ligating to Fe(2+) and DHPA bound with Fe(2+) in an octahedral coordination. In addition to DHPA, AbDHPAO can also use other 3,4-dihydroxyphenylacetate derivatives with different aliphatic carboxylic acid substituents as substrates, albeit with low reactivity. Altogether, this report provides a better understanding of the structure and biochemical properties of AbDHPAO and its homologs, which is advancing further modification of DHPAO in future applications. Structure and biochemical characterization of an extradiol 3,4-dihydroxyphenylacetate 2,3-dioxygenase from Acinetobacter baumannii.,Pimviriyakul P, Buttranon S, Soithongcharoen S, Supawatkon C, Disayabootr K, Watthaisong P, Tinikul R, Jaruwat A, Chaiyen P, Chitnumsub P, Maenpuen S Arch Biochem Biophys. 2023 Oct 1;747:109768. doi: 10.1016/j.abb.2023.109768. Epub , 2023 Sep 26. PMID:37769893[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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