Structure of a fungal form of aspartate-semialdehyde dehydrogenase from Aspergillus fumigatus
Aspartate-semialdehyde dehydrogenase (ASADH) functions at a critical junction in the aspartate biosynthetic pathway and represents a validated target for antimicrobial drug design. This enzyme catalyzes the NADPH-dependent reductive dephosphorylation of β-aspartyl phosphate to produce the key intermediate aspartate semialdehyde. The absence of this entire pathway in humans and other mammals will allow the selective targeting of pathogenic microorganisms for antimicrobial development. Here, the X-ray structure of a new form of ASADH from the pathogenic fungal speciesAspergillus fumigatushas been determined. The overall structure of this enzyme is similar to those of its bacterial orthologs, but there are some critical differences both in biological assembly and in secondary-structural features that can potentially be exploited for the development of species-selective drugs with selective toxicity against infectious fungal organisms.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- NIH
- OSTI ID:
- 1499796
- Journal Information:
- Acta Crystallographica. Section F, Structural Biology Communications, Journal Name: Acta Crystallographica. Section F, Structural Biology Communications Journal Issue: 1 Vol. 73; ISSN ACSFEN; ISSN 2053-230X
- Publisher:
- International Union of Crystallography
- Country of Publication:
- United States
- Language:
- ENGLISH
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