3N9R

Class II fructose-1,6-bisphosphate aldolase from helicobacter pylori in complex with N-(4-hydroxybutyl)-phosphoglycolohydroxamic acid, a competitive inhibitor

Summary for 3N9R

• Entry DOI: 10.2210/pdb3n9r/pdb
• Related: 3C4U 3C52 3C56 3N9S
• Descriptor: Fructose-bisphosphate aldolase, ZINC ION, SODIUM ION, ... (6 entities in total)
• Functional Keywords: fbp aldolase, class ii, inhibitor, lyase
• Biological source: Helicobacter pylori
• Total number of polymer chains: 8
• Total formula weight: 273342.53

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

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: 20929256
DOI: 10.1021/jm1009814

Experimental method

X-RAY DIFFRACTION (1.8 Å)