Download MendeleyExpansion of the aspartate beta-semialdehyde dehydrogenase family: the first structure of a fungal ortholog.
Arachea, B.T., Liu, X., Pavlovsky, A.G., Viola, R.E.(2010) Acta Crystallogr D Biol Crystallogr 66: 205-212
- PubMed: 20124701
- DOI: https://doi.org/10.1107/S0907444909052834
- Primary Citation of Related Structures:
3HSK - PubMed 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.
Organizational Affiliation:
Department of Chemistry, University of Toledo, Toledo, Ohio 43606, USA.
