Characterization of sequence and structural features of the Candida krusei enolase.
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.
Western Australian Biomedical Research Institute, Perth, Australia.
Neha S
NS
Gandhi
Kathy
K
Young
John R
JR
Warmington
Ricardo L
RL
Mancera
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002175:Candida / Q000201:enzymology* / Q000235:genetics; D020134:Catalytic Domain; D006801:Humans; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010751:Phosphopyruvate Hydratase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D013379:Substrate Specificity
D010958:Plasminogen; D010751:Phosphopyruvate Hydratase; D008274:Magnesium