5IFI
CRYSTAL STRUCTURE OF ACETYL-COA SYNTHETASE IN COMPLEX WITH ADENOSINE-5'-PROPYLPHOSPHATE FROM CRYPTOCOCCUS NEOFORMANS H99
Summary for 5IFI
| Entry DOI | 10.2210/pdb5ifi/pdb |
| Descriptor | Acetyl-coenzyme A synthetase, ADENOSINE-5'-MONOPHOSPHATE-PROPYL ESTER, 1,2-ETHANEDIOL, ... (5 entities in total) |
| Functional Keywords | ssgcid, nih, niaid, sbri, uw, beryllium, synthetase, acs1, prx, propyl-amp, structural genomics, seattle structural genomics center for infectious disease, ligase |
| Biological source | Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 / CBS 10515 / FGSC 9487) |
| Total number of polymer chains | 3 |
| Total formula weight | 235092.26 |
| Authors | Seattle Structural Genomics Center for Infectious Disease (SSGCID),SSGCID,Fox III, D.,Edwards, T.E.,Lorimer, D.D.,Mutz, M.W. (deposition date: 2016-02-26, release date: 2016-03-16, Last modification date: 2025-09-10) |
| Primary citation | Daraji, D.G.,Jezewski, A.J.,Alden, K.M.,Propp, J.P.,Heene, M.E.,Soldan, C.A.,Liu, L.,Battaile, K.P.,Lovell, S.,Staker, B.L.,Krysan, D.J.,Hagen, T.J. Synthesis and evaluation of acyl-AMP phosphate isosteres as inhibitors of fungal acetyl CoA synthetase. Bioorg.Med.Chem.Lett., :130389-130389, 2025 Cited by PubMed Abstract: Acetyl-CoA synthetase (ACS) is a member of the adenylate-forming enzymes superfamily. This enzyme plays a crucial role in cellular metabolism. While ACS enzymes are non-essential in mammals, they are essential in some fungal species and parasites that are pathogenic to humans. Hence, inhibition of the ACS enzyme is an emerging target for the development of novel anti-infectives. Alkyl AMP esters and acyl sulfamoyl adenosine (Acyl-AMS) are potent inhibitors of fungal ACS enzymes by mimicingthe acyl-AMP enzyme intermediate. Molecular docking studies were performed to facilitate the design of analogs and to explore their potential ligand-binding interactions with the ACS enzyme. A series of acyl-AMP isosteres were synthesized and screened for inhibitory activity against fungal ACS enzymes. Notably, Compound 14 was successfully crystallized with the Cryptococcus neoformans ACS1 enzyme, providing valuable structural insight for future inhibitor design. PubMed: 40885291DOI: 10.1016/j.bmcl.2025.130389 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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