5IFI

CRYSTAL STRUCTURE OF ACETYL-COA SYNTHETASE IN COMPLEX WITH ADENOSINE-5'-PROPYLPHOSPHATE FROM CRYPTOCOCCUS NEOFORMANS H99

5IFI の概要

• エントリーDOI: 10.2210/pdb5ifi/pdb
• 分子名称: Acetyl-coenzyme A synthetase, ADENOSINE-5'-MONOPHOSPHATE-PROPYL ESTER, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: ssgcid, nih, niaid, sbri, uw, beryllium, synthetase, acs1, prx, propyl-amp, structural genomics, seattle structural genomics center for infectious disease, ligase
• 由来する生物種: Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 / CBS 10515 / FGSC 9487)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 235092.26

構造登録者

Seattle Structural Genomics Center for Infectious Disease (SSGCID),SSGCID,Fox III, D.,Edwards, T.E.,Lorimer, D.D.,Mutz, M.W. (登録日: 2016-02-26, 公開日: 2016-03-16, 最終更新日: 2025-09-10)

主引用文献

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

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: 40885291
DOI: 10.1016/j.bmcl.2025.130389

実験手法

X-RAY DIFFRACTION (1.95 Å)