Biomaterial Database

Salivary histatin 5: dependence of sequence, chain length, and helical conformation for candidacidal activity. 1990

P A Raj, and M Edgerton, and M J Levine

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

Histatin 5 (Asp1-Ser-His-Ala4-Lys-Arg-His-His8-Gly-Tyr-Lys-Arg12-Lys-Ph e-His-Glu16-Lys-His - His-Ser20-His-Arg-Gly-Tyr24), one of the basic histidine-rich peptides present in human parotid saliva and several of its fragments, 1-16 (N16), 9-24 (C16), 11-24 (C14), 13-24 (C12), 15-24 (C10), and 7-16 (M10), were synthesized by solid-phase procedures. Native histatin 5 from human parotid saliva was also purified. Their antifungal activities on two strains of Candida albicans have been studied and their conformational preferences both in aqueous and non-aqueous solutions examined by circular dichroism. The synthetic histatin 5, C16, and C14 peptides were highly active and inhibited the growth of C. albicans. The candidacidal activity data of synthetic histatin 5 were comparable to the values of the native histatin 5 isolated from parotid saliva and those reported previously, although the assay system used and the strains examined were different. The C16 fragment was as active as the whole peptide itself, whereas the N16 fragment was far less active than C14, suggesting that the sequence at the C-terminal is important for its fungicidal activity. An increase in the chain length of the C-terminal sequence from 12 to 16 residues increased the candidacidal activity, thereby indicating that a peptide chain length of at least 12 residues is necessary to elicit optimum biological activity. The CD spectra of these linear peptides showed that they are structurally more flexible, and they adopt different conformations depending on the solvent environment. CD studies provided evidence that histatin 5 and the longer fragments, C16, N16, and C14 preferred alpha-helical conformations in non-aqueous solvents such as trifluoroethanol and methanol, while in water and pH 7.4 phosphate buffers, they favored random coil structures. The shorter sequences seemed to adopt either turn structures or unordered structures both in aqueous and non-aqueous solutions. It appears that the sequence at the C-terminal of histatin 5 with a minimum chain length of 14 residues and alpha-helical conformation are the important structural requirements for appreciable candidacidal activity.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010306	Parotid Gland	The largest of the three pairs of SALIVARY GLANDS. They lie on the sides of the FACE immediately below and in front of the EAR.	Gland, Parotid,Glands, Parotid,Parotid Glands
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D002176	Candida albicans	A unicellular budding fungus which is the principal pathogenic species causing CANDIDIASIS (moniliasis).	Candida albicans var. stellatoidea,Candida stellatoidea,Dematium albicans,Monilia albicans,Myceloblastanon albicans,Mycotorula albicans,Parasaccharomyces albicans,Procandida albicans,Procandida stellatoidea,Saccharomyces albicans,Syringospora albicans
D002942	Circular Dichroism	A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	Circular Dichroism, Vibrational,Dichroism, Circular,Vibrational Circular Dichroism
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein