4zhs

Crystal Structure of Aspartate Semialdehyde Dehydrogenase from Trichophyton rubrum

spinqualitylabelsall models 4zhs, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4zhs is a 6 chain structure with sequence from Trichophyton rubrum BMU01672. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MSE, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A140UHG6_TRIRU Publication Abstract from PubMed Aspartate-beta-semialdehyde dehydrogenase (ASADH) catalyzes the second reaction in the aspartate pathway, a pathway required for the biosynthesis of one fifth of the essential amino acids in plants and microorganisms. Microarray analysis of a fungal pathogen T. rubrum responsible for most human dermatophytoses identified the upregulation of ASADH (trASADH) expression when the fungus is exposed to human skin, underscoring its potential as a drug target. Here we report the crystal structure of trASADH, revealing a tetrameric ASADH with a GAPDH-like fold. The tetramerization of trASADH was confirmed by sedimentation and SAXS experiments. Native PAGE demonstrated that this ASADH tetramerization is apparently universal in fungal species, unlike the functional dimer that is observed in all bacterial ASADHs. The helical subdomain in dimeric bacteria ASADH is replaced by the cover loop in archaeal/fungal ASADHs, presenting the determinant for this altered oligomerization. Mutations that disrupt the tetramerization of trASADH also abolish the catalytic activity, suggesting that the tetrameric state is required to produce the active fungal enzyme form. Our findings provide a basis to categorize ASADHs into dimeric and tetrameric enzymes, adopting a different orientation for NADP binding and offer a structural framework for designing drugs that can specifically target the fungal pathogens. Structural Insights into the Tetrameric State of Aspartate-beta-semialdehyde Dehydrogenases from Fungal Species.,Li Q, Mu Z, Zhao R, Dahal G, Viola RE, Liu T, Jin Q, Cui S Sci Rep. 2016 Feb 12;6:21067. doi: 10.1038/srep21067. PMID:26869335 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aspartate-semialdehyde dehydrogenase 3D structures Retinoid X receptor 3D structures

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