2w5u

Flavodoxin from Helicobacter pylori in complex with the C3 inhibitor

spinqualitylabelsall models 2w5u, resolution 2.62Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2w5u is a 2 chain structure with sequence from Helicobacter pylori. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.62Å Ligands: FMN, IC3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FLAV_HELPY Low-potential electron donor to a number of redox enzymes (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Helicobacter pylori establishes life-long infections in the gastric mucosa of over 1 billion people worldwide. In many cases, without specific antimicrobial intervention, H. pylori infected individuals will develop type B gastritis, chronic peptic ulcers and, more rarely, gastric neoplasias. Conventional antimicrobial therapy has been complicated by dramatic increases in resistance to macrolides, metronidazole and fluoroquinolones. Here, we report the development of novel therapeutics that specifically target the unique flavodoxin component of an essential metabolic pathway of H. pylori. With the use of high-throughput screening methodology, we have tested 10,000 chemicals and have identified 29 compounds that bind flavodoxin, four of which interrupted in vitro electron transfer to flavodoxin physiological partners. Three of these compounds are bactericidal and promisingly selective for H. pylori. The minimal inhibitory concentrations of two of them are 10 times lower than their minimal cytotoxic concentrations for HeLa cells. Importantly, neither of the four inhibitors is toxic for mice after administration of 1-10 mg kg(-1) doses twice a day for 5 days. Enzymatic, thermodynamic and structural characterization of the inhibitor-flavodoxin complexes suggests these compounds could act by modifying the redox potentials of flavodoxin. These newly discovered inhibitors represent promising selective leads against the different diseases associated to H. pylori infection. Discovery of specific flavodoxin inhibitors as potential therapeutic agents against Helicobacter pylori infection.,Cremades N, Velazquez-Campoy A, Martinez-Julvez M, Neira JL, Perez-Dorado I, Hermoso J, Jimenez P, Lanas A, Hoffman PS, Sancho J ACS Chem Biol. 2009 Nov 20;4(11):928-38. PMID:19725577 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Flavodoxin 3D structures

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