6OKC
Crosslinked Crystal Structure of Type II Fatty Acid Synthase Ketosynthase, FabB, and C12-crypto Acyl Carrier Protein, AcpP
Summary for 6OKC
| Entry DOI | 10.2210/pdb6okc/pdb |
| Descriptor | 3-oxoacyl-[acyl-carrier-protein] synthase 1, Acyl carrier protein, N-[2-(dodecanoylamino)ethyl]-N~3~-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alaninamide, ... (4 entities in total) |
| Functional Keywords | thiolase, ketosynthase, ks, acpp, transferase-lipid transport complex, transferase/lipid transport |
| Biological source | Escherichia coli (strain K12) More |
| Total number of polymer chains | 4 |
| Total formula weight | 103650.53 |
| Authors | Mindrebo, J.T.,Kim, W.E.,Bartholow, T.G.,Chen, A.,Davis, T.D.,La Clair, J.,Burkart, M.D.,Noel, J.P. (deposition date: 2019-04-12, release date: 2020-04-15, Last modification date: 2024-11-06) |
| Primary citation | Mindrebo, J.T.,Patel, A.,Kim, W.E.,Davis, T.D.,Chen, A.,Bartholow, T.G.,La Clair, J.J.,McCammon, J.A.,Noel, J.P.,Burkart, M.D. Gating mechanism of elongating beta-ketoacyl-ACP synthases. Nat Commun, 11:1727-1727, 2020 Cited by PubMed Abstract: Carbon-carbon bond forming reactions are essential transformations in natural product biosynthesis. During de novo fatty acid and polyketide biosynthesis, β-ketoacyl-acyl carrier protein (ACP) synthases (KS), catalyze this process via a decarboxylative Claisen-like condensation reaction. KSs must recognize multiple chemically distinct ACPs and choreograph a ping-pong mechanism, often in an iterative fashion. Here, we report crystal structures of substrate mimetic bearing ACPs in complex with the elongating KSs from Escherichia coli, FabF and FabB, in order to better understand the stereochemical features governing substrate discrimination by KSs. Complemented by molecular dynamics (MD) simulations and mutagenesis studies, these structures reveal conformational states accessed during KS catalysis. These data taken together support a gating mechanism that regulates acyl-ACP binding and substrate delivery to the KS active site. Two active site loops undergo large conformational excursions during this dynamic gating mechanism and are likely evolutionarily conserved features in elongating KSs. PubMed: 32265440DOI: 10.1038/s41467-020-15455-x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
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