29VZ
Structure of Tetrahydrocannabinolic acid synthase(THCAS) in complex with FAD
Summary for 29VZ
| Entry DOI | 10.2210/pdb29vz/pdb |
| Descriptor | Cannabichromenic acid synthase (Fragment), FLAVIN-ADENINE DINUCLEOTIDE, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | cannabinoid, fad, synthase, oxidoreductase |
| Biological source | Cannabis sativa |
| Total number of polymer chains | 1 |
| Total formula weight | 63561.96 |
| Authors | Domenech, J.,Cartwright, J.,Grogan, G. (deposition date: 2026-04-10, release date: 2026-07-29, Last modification date: 2026-08-05) |
| Primary citation | Domenech, J.,King, A.,Byrne, E.,Cartwright, J.,Grogan, G. X-ray crystal structures of the cannabinoid synthases CBCAS, CBDAS and THCAS. Curr Res Struct Biol, 12:100197-100197, 2026 Cited by PubMed Abstract: The enzymes Cannabichromenic Acid Synthase (CBCAS), Cannabidiolic Acid Synthase (CBDAS) and Tetrahydrocannabinolic Acid Synthase (THCAS) are together the major cannabinoid synthase enzymes responsible for the biosynthesis of their respective metabolites from a common precursor Cannabigerolic Acid (CBGA). As the catalysts responsible for generating biological molecules of significant pharmaceutical value, there has been considerable interest in the enzymes with respect to heterologous production, mechanism, and incorporation into synthetic biology pathways for the facile industrial production of these molecules. The enzymes share high degrees of homology, and therefore their distinct specificities are governed by very subtle differences in sequence and therefore structure, although, until now, only a structure for THCAS has been reported. In this report, we present structures of CBCAS, CBDAS and a structure of THCAS at a higher resolution than the known structure, each in complex with their flavin coenzyme FAD. The structures reveal active site differences that may be responsible for the complementary activities observed, in terms of both first-shell amino acid substitutions, but also in more remote residues that influence active site topology through referred effects, or that have effects on substrate access. The structures provide a useful and informative platform for the rational engineering of improved or altered chemoselectivity in these enzymes. PubMed: 42502799DOI: 10.1016/j.crstbi.2026.100197 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.43 Å) |
Structure validation
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