2w3n

Structure and inhibition of the CO2-sensing carbonic anhydrase Can2 from the pathogenic fungus Cryptococcus neoformans

spinqualitylabelsall models 2w3n, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2w3n is a 3 chain structure with sequence from Atcc 32045. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, GOL, ZN Activity: Carbonate dehydratase, with EC number 4.2.1.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 In the pathogenic fungus Cryptococcus neoformans, a CO(2)-sensing system is essential for survival in the natural environment ( approximately 0.03% CO(2)) and mediates the switch to virulent growth in the human host ( approximately 5% CO(2)). This system is composed of the carbonic anhydrase (CA) Can2, which catalyzes formation of bicarbonate, and the fungal, bicarbonate-stimulated adenylyl cyclase Cac1. The critical role of these enzymes for fungal metabolism and pathogenesis identifies them as targets for antifungal drugs. Here, we prove functional similarity of Can2 to the CA Nce103 from Candida albicans and describe its biochemical and structural characterization. The crystal structure of Can2 reveals that the enzyme belongs to the "plant-type" beta-CAs but carries a unique N-terminal extension that can interact with the active-site entrance of the dimer. We further tested a panel of compounds, identifying nanomolar Can2 inhibitors, and present the structure of a Can2 complex with the inhibitor and product analog acetate, revealing insights into interactions with physiological ligands and inhibitors. Structure and Inhibition of the CO(2)-Sensing Carbonic Anhydrase Can2 from the Pathogenic Fungus Cryptococcus neoformans.,Schlicker C, Hall RA, Vullo D, Middelhaufe S, Gertz M, Supuran CT, Muhlschlegel FA, Steegborn C J Mol Biol. 2008 Nov 27. PMID:19071134 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carbonic anhydrase 3D structures

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