Candidacidal activity of recombinant human salivary histatin-5 and variants.
AUTOR(ES)
Tsai, H
RESUMO
Human salivary histatins possess fungicidal and bactericidal activities. The current investigation evaluates the structure-function relationship of histatins with regard to their candidacidal activity by using recombinant histatin-5 and its variants produced in Escherichia coli. The purified recombinant histatins were examined for their candidacidal activity and secondary structure. The m21 (with Lys-13 replaced by Thr [Lys-13-->Thr]) and m71 (Lys-13-->Glu) variants are significantly less effective than recombinant histatin-5 in killing Candida albicans, suggesting that Lys-13 is critical for candidacidal activity. The m68 (Lys-13-->Glu and Arg-22-->Gly) variant is significantly less potent than the recombinant histatin-5 as well as m71, indicating that Arg-22 is crucial for the cidal activity. The candidacidal activities of m1 (Arg-12-->Ile), m2 (Arg-12-->Ile and Lys-17-->Asp), m12 (Arg-12-->Lys and His-21-->Leu), and m70 (His-19-->Pro and His-21-->Arg) variants, however, are comparable to that of recombinant histatin-5, indicating that Arg-12, Lys-17, His-19, and His-21 are not functionally important. The conformational preferences of histatin-5 and variants were determined by circular dichroism. The results indicate that all proteins have a strong tendency to adopt alpha-helical conformation in trifluoroethanol. Previously, we have shown that the alpha-helical conformation is one of the important structural requirements for eliciting appreciable candidacidal activity. Collectively, the data suggest that in addition to the helical conformation, specific residues such as Lys-13 and Arg-22 in the sequence of histatin-5 are, indeed, important for candidacidal activity.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=174480Documentos Relacionados
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