3N9S
Class II fructose-1,6-bisphosphate aldolase from helicobacter pylori in complex with N-(4-hydroxybutyl)- glycolohydroxamic acid bis-phosphate, a competitive inhibitor
Summary for 3N9S
| Entry DOI | 10.2210/pdb3n9s/pdb |
| Related | 3C4U 3C52 3C56 3N9R |
| Descriptor | Fructose-bisphosphate aldolase, 4-{hydroxy[(phosphonooxy)acetyl]amino}butyl dihydrogen phosphate, ZINC ION, ... (6 entities in total) |
| Functional Keywords | fbp aldolase, class ii, inhibitor, lyase, lyase-lyase inhibitor complex, lyase/lyase inhibitor |
| Biological source | Helicobacter pylori |
| Total number of polymer chains | 2 |
| Total formula weight | 68504.84 |
| Authors | Coincon, M.,Sygusch, S. (deposition date: 2010-05-31, release date: 2010-11-17, Last modification date: 2023-09-06) |
| Primary citation | Daher, R.,Fonvielle, M.,Gest, P.M.,Guerin, M.E.,Jackson, M.,Sygusch, J.,Therisod, M. Rational Design, Synthesis, and Evaluation of New Selective Inhibitors of Microbial Class II (Zinc Dependent) Fructose Bis-phosphate Aldolases. J.Med.Chem., 53:7836-7842, 2010 Cited by PubMed Abstract: We report the synthesis and biochemical evaluation of several selective inhibitors of class II (zinc dependent) fructose bis-phosphate aldolases (Fba). The products were designed as transition-state analogues of the catalyzed reaction, structurally related to the substrate fructose bis-phosphate (or sedoheptulose bis-phosphate) and based on an N-substituted hydroxamic acid, as a chelator of the zinc ion present in active site. The compounds synthesized were tested on class II Fbas from various pathogenic microorganisms and, by comparison, on a mammalian class I Fba. The best inhibitor shows K(i) against class II Fbas from various pathogens in the nM range, with very high selectivity (up to 10(5)). Structural analyses of inhibitors in complex with aldolases rationalize and corroborate the enzymatic kinetics results. These inhibitors represent lead compounds for the preparation of new synthetic antibiotics, notably for tuberculosis prophylaxis. PubMed: 20929256DOI: 10.1021/jm1009814 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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