8ZEC

AtoB in complex with substrate analogue

This is a non-PDB format compatible entry.

Summary for 8ZEC

• Entry DOI: 10.2210/pdb8zec/pdb
• Descriptor: Crystal structure of aldolase AtoB complex with substrate analogue, (1S,2R,3S,12R,13S,16R)-2,16-dihydroxy-3,6,7,13,17,17-hexamethyl-4,8,19-trioxatetracyclo[14.2.1.03,12.05,10]nonadeca-5(10),6-diene-9,18-dione, SULFATE ION, ... (5 entities in total)
• Functional Keywords: biosynthetic protein
• Biological source: Aspergillus ochraceus
• Total number of polymer chains: 2
• Total formula weight: 35588.21

Authors

Ma, K.,Fan, A.,Lin, W. (deposition date: 2024-05-05, release date: 2025-05-14, Last modification date: 2025-11-26)

Primary citation

Ma, K.,Liu, J.,Huang, Z.,Wu, M.,Liu, D.,Ren, J.,Fan, A.,Lin, W.
Three-dimensional structural alignment based discovery and molecular basis of AtoB, catalyzing linear tetracyclic formation.
Chem Sci, 15:18490-18496, 2024

PubMed Abstract: 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 Å and 1.6 Å resolution, respectively, revealing the rotation of the α4 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.

PubMed: 39430940
DOI: 10.1039/d4sc05590j

Experimental method

X-RAY DIFFRACTION (1.65 Å)