title: Expansion of the aspartate beta-semialdehyde dehydrogenase family: the first structure of a fungal ortholog.
abstract: The enzyme aspartate semialdehyde dehydrogenase (ASADH) catalyzes a critical transformation that produces the first branch-point intermediate in an essential microbial amino-acid biosynthetic pathway. The first structure of an ASADH isolated from a fungal species (Candida albicans) has been determined as a complex with its pyridine nucleotide cofactor. This enzyme is a functional dimer, with a similar overall fold and domain organization to the structurally characterized bacterial ASADHs. However, there are differences in the secondary-structural elements and in cofactor binding that are likely to cause the lower catalytic efficiency of this fungal enzyme. Alterations in the dimer interface, through deletion of a helical subdomain and replacement of amino acids that participate in a hydrogen-bonding network, interrupt the intersubunit-communication channels required to support an alternating-site catalytic mechanism. The detailed functional information derived from this new structure will allow an assessment of ASADH as a possible target for antifungal drug development.
authors.affiliation: Department of Chemistry, University of Toledo, Toledo, Ohio 43606, USA.
authors.forename: Buenafe T
authors.initials: BT
authors.lastname: Arachea
authors.forename: Xuying
authors.initials: X
authors.lastname: Liu
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Pavlovsky
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Viola
mesh_terms: D000595:Amino Acid Sequence; D001223:Aspartate-Semialdehyde Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D002176:Candida albicans / Q000201:enzymology*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D001223:Aspartate-Semialdehyde Dehydrogenase