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Publication Abstract from PubMed

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.

Expansion of the aspartate beta-semialdehyde dehydrogenase family: the first structure of a fungal ortholog.,Arachea BT, Liu X, Pavlovsky AG, Viola RE Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):205-12. Epub 2010, Jan 22. PMID:20124701^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.