5X6F
Crystal structure of Phosphopantetheine adenylyltransferase from Pseudomonas aeruginosa
Summary for 5X6F
| Entry DOI | 10.2210/pdb5x6f/pdb |
| Descriptor | Phosphopantetheine adenylyltransferase, ISOPROPYL ALCOHOL, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | phosphopantetheine adenylyltransferase, pseudomonas aeruginosa, transferase |
| Biological source | Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) |
| Cellular location | Cytoplasm : Q9I6D1 |
| Total number of polymer chains | 6 |
| Total formula weight | 107353.50 |
| Authors | Mondal, A.,Chatterjee, R.,Datta, S. (deposition date: 2017-02-21, release date: 2018-02-14, Last modification date: 2024-03-27) |
| Primary citation | Mondal, A.,Chatterjee, R.,Datta, S. Umbrella Sampling and X-ray Crystallographic Analysis Unveil an Arg-Asp Gate Facilitating Inhibitor Binding Inside Phosphopantetheine Adenylyltransferase Allosteric Cleft. J Phys Chem B, 122:1551-1559, 2018 Cited by PubMed Abstract: Phosphopantetheine adenylyltransferase (PPAT) is a rate-limiting enzyme essential for biosynthesis of coenzyme A (CoA), which in turn is responsible to regulate the secretion of exotoxins via type III secretion system in Pseudomonas aeruginosa, causing severe health concerns ranging from nosocomial infections to respiratory failure. Acetyl coenzyme A (AcCoA) is a newly reported inhibitor of PPAT, believed to regulate the cellular levels of CoA and thereby the pathogenesis. Very little is known so far regarding the mechanistic details of AcCoA binding inside PPAT-binding cleft. Herein, we have used extensive umbrella sampling simulations to decipher mechanistic insight into the inhibitor accommodation inside the binding cavity. We found that R90 and D94 residues act like a gate near the binding cavity to accommodate and stabilize the incoming ligand. Mutational models concerning these residues also show considerable difference in AcCoA-binding thermodynamics. To substantiate our findings, we have solved the first crystal structure of apo-PPAT from P. aeruginosa, which also found to agree with the simulation results. Collectively, these results describe the mechanistic details of accommodation of inhibitor molecule inside PPAT-binding cavity and also offer valuable insight into regulating cellular levels of CoA/AcCoA and thus controlling the pathogenicity. PubMed: 29345931DOI: 10.1021/acs.jpcb.7b09543 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.593 Å) |
Structure validation
Download full validation report
