Format

Send to

Choose Destination
See comment in PubMed Commons below
Infect Immun. 1996 Dec;64(12):5000-7.

Candidacidal activity of recombinant human salivary histatin-5 and variants.

Author information

1
Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, 14214, USA.

Abstract

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.

PMID:
8945538
PMCID:
PMC174480
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center