Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-2-26
pubmed:abstractText
Chemokines are small (8-12 kDa) effector proteins that potentiate leukocyte chemonavigation. Beyond this role, certain chemokines have direct antimicrobial activity against human pathogenic organisms; such molecules are termed kinocidins. The current investigation was designed to explore the structure-activity basis for direct microbicidal activity of kinocidins. Amino acid sequence and 3-dimensional analyses demonstrated these molecules to contain iterations of the conserved gamma-core motif found in broad classes of classical antimicrobial peptides. Representative CXC, CC and C cysteine-motif-group kinocidins were tested for antimicrobial activity versus human pathogenic bacteria and fungi. Results demonstrate that these molecules exert direct antimicrobial activity in vitro, including antibacterial activity of native IL-8 and MCP-1, and microbicidal activity of native IL-8. To define molecular determinants governing its antimicrobial activities, the IL-8 gamma-core (IL-8gamma) and alpha-helical (IL-8alpha) motifs were compared to native IL-8 for antimicrobial efficacy in vitro. Microbicidal activity recapitulating that of native IL-8 localized to the autonomous IL-8alpha motif in vitro, and demonstrated durable microbicidal activity in human blood and blood matrices ex vivo. These results offer new insights into the modular architecture, context-related deployment and function, and evolution of host defense molecules containing gamma-core motifs and microbicidal helices associated with antimicrobial activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:volume
1768
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
598-608
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17208195-Amino Acid Motifs, pubmed-meshheading:17208195-Amino Acid Sequence, pubmed-meshheading:17208195-Anti-Bacterial Agents, pubmed-meshheading:17208195-Candida albicans, pubmed-meshheading:17208195-Chemokines, pubmed-meshheading:17208195-Circular Dichroism, pubmed-meshheading:17208195-Colony Count, Microbial, pubmed-meshheading:17208195-Conserved Sequence, pubmed-meshheading:17208195-Cysteine, pubmed-meshheading:17208195-Humans, pubmed-meshheading:17208195-Hydrogen-Ion Concentration, pubmed-meshheading:17208195-Interleukin-8, pubmed-meshheading:17208195-Microbial Sensitivity Tests, pubmed-meshheading:17208195-Models, Molecular, pubmed-meshheading:17208195-Molecular Sequence Data, pubmed-meshheading:17208195-Peptides, pubmed-meshheading:17208195-Protein Structure, Secondary, pubmed-meshheading:17208195-Protein Structure, Tertiary, pubmed-meshheading:17208195-Recombinant Proteins, pubmed-meshheading:17208195-Salmonella typhimurium, pubmed-meshheading:17208195-Sequence Homology, Amino Acid, pubmed-meshheading:17208195-Spectrophotometry, pubmed-meshheading:17208195-Staphylococcus aureus, pubmed-meshheading:17208195-Structure-Activity Relationship
pubmed:year
2007
pubmed:articleTitle
Structural correlates of antimicrobial efficacy in IL-8 and related human kinocidins.
pubmed:affiliation
Division of Infectious Diseases, LAC-Harbor UCLA Medical Center, Torrance, CA 90509, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural