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Publication Abstract from PubMed

Enzymes from the nuclear transport factor 2-like (NTF2-like) superfamily represent a rare group of biocatalysts with diverse catalytic functions facilitating intriguing skeleton formations. However, most proteins of this family remain enigmatic and await further elucidation. In this study, a combination of protein structural alignment with clustering analysis uncovers a new aldolase, AtoB, belonging to the NTF2-like superfamily. AtoB catalyzes the key intramolecular aldol reaction in linear tetracyclic meroterpenoid biosynthesis. The X-ray crystal structures of AtoB and AtoB-ligand complex are established at 1.9 A and 1.6 A resolution, respectively, revealing the rotation of the alpha4 helix and key residues in the active site for substrate binding. Molecular docking and site-directed mutagenesis demonstrate an acid-base pair involved in the AtoB-catalyzed aldol reaction, of which Arg59 is responsible for stereocontrol of hydroxylated C-10a during condensation. These findings provide valuable information for understanding the catalytic mechanisms of the AtoB-catalyzed aldol reaction. Additionally, a branching biosynthetic pathway of aspertetranones is elucidated during the exploration of the natural substrate of AtoB.

Three-dimensional structural alignment based discovery and molecular basis of AtoB, catalyzing linear tetracyclic formation.,Ma K, Liu J, Huang Z, Wu M, Liu D, Ren J, Fan A, Lin W Chem Sci. 2024 Oct 11;15(44):18490-6. doi: 10.1039/d4sc05590j. PMID:39430940^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.