2nlf
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Human beta-defensin-1 (Mutant Leu13Glu)
OverviewOverview
Defensins are small (30-45 amino acid residues) cationic proteins with, broad antimicrobial activity against many bacteria and fungi, some, enveloped viruses, and other activities such as chemoattraction of a range, of different cell types to the sites of inflammation. These proteins, represent attractive targets for developing novel antimicrobial agents and, modulators of immune responses with therapeutic applicability. In this, report, we present the results of functional and structural studies of 26, single-site mutants of human beta-defensin 1 (hBD1). All mutants were, assayed for antimicrobial activity against Escherichia coli (ATCC strain, 25922) and for chemotactic activity with CCR6-transfected HEK293 cells. To, analyze the structural implications of mutagenesis and to verify the, correctness of the disulfide connectivity, we used x-ray crystallography, to conduct complete structural studies for 10 mutants in which the, topology of disulfides was the same as in the native hBD1. Mutations did, not induce significant changes of the tertiary structure, suggesting that, the observed alterations of biological properties of the mutants were, solely associated with changes in the respective side chains. We found, that cationic residues located near the C terminus (Arg(29), Lys(31), Lys(33), and Lys(36)) of hBD1 define most of the anti-E. coli in vitro, activity of this protein. In turn, nearly all mutations altering the, CCR6-mediated chemotaxis are located at one area of the protein, defined, by the N-terminal alpha-helical region (Asp(1)... Ser(8)) and a few, topologically adjacent residues (Lys(22), Arg(29), and Lys(33)). These, experimental results allow for the first time drafting of the CCR6-epitope, for a defensin molecule.
About this StructureAbout this Structure
2NLF is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Studies of the biological properties of human beta-defensin 1., Pazgier M, Prahl A, Hoover DM, Lubkowski J, J Biol Chem. 2007 Jan 19;282(3):1819-29. Epub 2006 Oct 27. PMID:17071614
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