4RPM
Crystal structure of the SAT domain from the non-reducing fungal polyketide synthase CazM with bound hexanoyl
Summary for 4RPM
| Entry DOI | 10.2210/pdb4rpm/pdb |
| Descriptor | SAT domain from CazM, HEXANOIC ACID, HEXANOYL-COENZYME A, ... (4 entities in total) |
| Functional Keywords | transferase |
| Biological source | Chaetomium globosum (Soil fungus) |
| Total number of polymer chains | 1 |
| Total formula weight | 45557.92 |
| Authors | Winter, J.M.,Cascio, D.,Sawaya, M.R.,Tang, Y. (deposition date: 2014-10-30, release date: 2015-09-09, Last modification date: 2024-10-16) |
| Primary citation | Winter, J.M.,Cascio, D.,Dietrich, D.,Sato, M.,Watanabe, K.,Sawaya, M.R.,Vederas, J.C.,Tang, Y. Biochemical and Structural Basis for Controlling Chemical Modularity in Fungal Polyketide Biosynthesis. J.Am.Chem.Soc., 137:9885-9893, 2015 Cited by PubMed Abstract: Modular collaboration between iterative fungal polyketide synthases (IPKSs) is an important mechanism for generating structural diversity of polyketide natural products. Inter-PKS communication and substrate channeling are controlled in large by the starter unit acyl carrier protein transacylase (SAT) domain found in the accepting IPKS module. Here, we reconstituted the modular biosynthesis of the benzaldehyde core of the chaetoviridin and chaetomugilin azaphilone natural products using the IPKSs CazF and CazM. Our studies revealed a critical role of CazM's SAT domain in selectively transferring a highly reduced triketide product from CazF. In contrast, a more oxidized triketide that is also produced by CazF and required in later stages of biosynthesis of the final product is not recognized by the SAT domain. The structural basis for the acyl unit selectivity was uncovered by the first X-ray structure of a fungal SAT domain, highlighted by a covalent hexanoyl thioester intermediate in the SAT active site. The crystal structure of SAT domain will enable protein engineering efforts aimed at mixing and matching different IPKS modules for the biosynthesis of new compounds. PubMed: 26172141DOI: 10.1021/jacs.5b04520 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.4 Å) |
Structure validation
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