Affiliations: Western Australian Biomedical Research Institute,
Perth, Australia | School of Biomedical Sciences, Perth,
Australia | School of Pharmacy, Curtin University of Technology,
Perth, Australia
Note: [] Corresponding author. Ricardo L. Mancera, School of Pharmacy,
Curtin University of Technology, GPO Box U1987 Perth, WA 6845, Australia. Tel.:
+61 892661017; Fax: +61 892662342; E-mail: [email protected]
Abstract: The incidence of human infections by the fungal pathogen Candida
species has been increasing in recent years. Enolase is an essential
protein in fungal metabolism. Sequence data is available for human and a number
of medically important fungal species. An understanding of the structural and
functional features of fungal enolases may provide the structural basis for
their use as a target for the development of new anti-fungal drugs. We have
obtained the sequence of the enolase of Candida krusei (C. krusei),
as it is a significant medically important fungal pathogen. We have then used
multiple sequence alignments with various enolase isoforms in order to identify
C. krusei specific amino acid residues. The phylogenetic tree of enolases
shows that the C. krusei enolase assembles on the tree with the fungal
genes. Importantly, C. krusei lacks four amino acids in the active site
compared to human enolase, as revealed by multiple sequence alignments. These
differences in the substrate binding site may be exploited for the design of
new anti-fungal drugs to selectively block this enzyme. The lack of the
important amino acids in the active site also indicates that C. krusei
enolase might have evolved as a member of a mechanistically diverse enolase
superfamily catalying somewhat different reactions.
