2VB9
beta-ketoacyl-ACP synthase I (KAS) from E. coli, apo structure
Summary for 2VB9
| Entry DOI | 10.2210/pdb2vb9/pdb |
| Related | 1DD8 1EK4 1F91 1FJ4 1FJ8 1G5X 1H4F 2AQ7 2AQB 2BUH 2BUI 2BYW 2BYX 2BYY 2BYZ 2BZ3 2BZ4 2VB7 2VB8 2VBA |
| Descriptor | 3-OXOACYL-[ACYL-CARRIER-PROTEIN] SYNTHASE 1, CHLORIDE ION (3 entities in total) |
| Functional Keywords | fatty acid biosynthesis, cytoplasm, antibiotic, transferase, acyltransferase, lipid synthesis, fatty acid synthesis |
| Biological source | ESCHERICHIA COLI |
| Total number of polymer chains | 4 |
| Total formula weight | 170695.72 |
| Authors | Pappenberger, G.,Schulz-Gasch, T.,Bailly, J.,Hennig, M. (deposition date: 2007-09-06, release date: 2007-12-25, Last modification date: 2023-12-13) |
| Primary citation | Pappenberger, G.,Schulz-Gasch, T.,Kusznir, E.,Mueller, F.,Hennig, M. Structure-Assisted Discovery of an Aminothiazole Derivative as a Lead Molecule for Inhibition of Bacterial Fatty-Acid Synthesis. Acta Crystallogr.,Sect.D, 63:1208-, 2007 Cited by PubMed Abstract: Fatty-acid synthesis in bacteria is of great interest as a target for the discovery of antibacterial compounds. The addition of a new acetyl moiety to the growing fatty-acid chain, an essential step in this process, is catalyzed by beta-ketoacyl-ACP synthase (KAS). It is inhibited by natural antibiotics such as cerulenin and thiolactomycin; however, these lack the requirements for optimal drug development. Structure-based biophysical screening revealed a novel synthetic small molecule, 2-phenylamino-4-methyl-5-acetylthiazole, that binds to Escherichia coli KAS I with a binding constant of 25 microM as determined by fluorescence titration. A 1.35 A crystal structure of its complex with its target reveals noncovalent interactions with the active-site Cys163 and hydrophobic residues of the fatty-acid binding pocket. The active site is accessible through an open conformation of the Phe392 side chain and no conformational changes are induced at the active site upon ligand binding. This represents a novel binding mode that differs from thiolactomycin or cerulenin interaction. The structural information on the protein-ligand interaction offers strategies for further optimization of this low-molecular-weight compound. PubMed: 18084068DOI: 10.1107/S0907444907049852 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
Download full validation report
