8X89
Crystal Structure of Streptococcus pneumoniae fabG
Summary for 8X89
| Entry DOI | 10.2210/pdb8x89/pdb |
| Descriptor | 3-oxoacyl-[acyl-carrier-protein] reductase (2 entities in total) |
| Functional Keywords | fatty acid synthesis, oxidoreductase |
| Biological source | Streptococcus pneumoniae |
| Total number of polymer chains | 4 |
| Total formula weight | 103175.42 |
| Authors | Xu, K.M. (deposition date: 2023-11-27, release date: 2024-10-16, Last modification date: 2024-10-30) |
| Primary citation | Xu, K.,Zhong, J.,Li, J.,Cao, Y.,Wei, L. Structure features of Streptococcus pneumoniae FabG and virtual screening of allosteric inhibitors. Front Mol Biosci, 11:1472252-1472252, 2024 Cited by PubMed Abstract: , a gram-positive bacterium, is responsible for diverse infections globally, and its antibiotic resistance presents significant challenges to medical advancements. It is imperative to employ various strategies to identify antibiotics. 3-oxoacyl-[acyl-carrier-protein] reductase (FabG) is a key component in the type II fatty acid synthase (FAS II) system, which is a developing target for new anti-streptococcal drugs. We first demonstrated the function of SpFabG and and the 2 Å SpFabG structure was elucidated using X-ray diffraction technique. It was observed that the NADPH binding promotes the transformation from tetramers to dimers in solution, suggesting dimers but not tetramer may be the active conformation. By comparing the structures of FabG homologues, we have identified the conserved tetramerization site and further confirmed the mechanism that the tetramerization site mutation leads to a loss of function and destabilization through mutagenesis experiments. Starting from 533,600 compounds, we proceeded with a sequential workflow involving pharmacophore-based virtual screening, molecular docking, and binding energy calculations. Combining all the structural analysis, we identified L1, L2 and L5 as a promising candidate for SpFabG inhibitor, based on the most stable binding mode in comparison to other evaluated inhibitors. PubMed: 39398278DOI: 10.3389/fmolb.2024.1472252 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.99 Å) |
Structure validation
Download full validation report
