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| | {{STRUCTURE_2o0s| PDB=2o0s | SCENE= }} | | {{STRUCTURE_2o0s| PDB=2o0s | SCENE= }} |
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| - | '''LPS-bound structure of a designed peptide'''
| + | ===LPS-bound structure of a designed peptide=== |
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| - | ==Overview==
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| - | Designing peptides that would interact with lipopolysaccharides (LPS) and acquire a specific folded conformation can generate useful structural insights toward the development of anti-sepsis agents. In this work, we have constructed a 12-residue linear peptide, YW12, rich in aromatic and aliphatic amino acid residues with a centrally located stretch of four consecutive positively charged (KRKR) residues. In absence of LPS, YW12 is predominantly unstructured in aqueous solution. Using transferred nuclear Overhauser effect (Tr-NOE) spectroscopy, we demonstrate that YW12 adopts a well-folded structure as a complex with LPS. Structure calculations reveal that YW12 assumes an extended conformation at the N-terminus followed by two consecutive beta-turns at its C-terminus. A hydrophobic core is formed by extensive packing between number of aromatic and nonpolar residues, whereas the positively charged residues are segregated out to a separate region essentially stabilizing an amphipathic structure. In an in vitro LPS neutralization assay using NF-kappaB induction as the readout, YW12 shows moderate activity with an IC50 value of approximately 10 microM. As would be expected, tryptophan fluorescence studies demonstrate that YW12 shows selective interactions only with the negatively charged lipid micelles including sodium dodecyl sulfate (SDS), 1-palmitoyl-2-oleoylphosphatidyl-dl-glycerol (POPG), and LPS, and no significant interactions are detected with zwitterionic lipid micelles such as dodecyl-phosphocholine (DPC). Far-UV CD studies indicate the presence of beta-turns or beta-sheet-like conformations of the peptide in negatively charged micelles, whereas no structural transitions are apparent in DPC micelles. These results suggest that structural features of YW12 could be utilized to develop nontoxic antisepsis compounds.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17469802}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17469802 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17469802}} |
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| | ==About this Structure== | | ==About this Structure== |
| - | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O0S OCA]. | + | Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O0S OCA]. |
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| | ==Reference== | | ==Reference== |
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| | [[Category: Lp]] | | [[Category: Lp]] |
| | [[Category: Peptide design]] | | [[Category: Peptide design]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:09:46 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:58:40 2008'' |
Revision as of 04:58, 28 July 2008
Template:STRUCTURE 2o0s
LPS-bound structure of a designed peptide
Template:ABSTRACT PUBMED 17469802
About this Structure
Full experimental information is available from OCA.
Reference
High-resolution solution structure of a designed peptide bound to lipopolysaccharide: transferred nuclear Overhauser effects, micelle selectivity, and anti-endotoxic activity., Bhattacharjya S, Domadia PN, Bhunia A, Malladi S, David SA, Biochemistry. 2007 May 22;46(20):5864-74. Epub 2007 May 1. PMID:17469802
Page seeded by OCA on Mon Jul 28 07:58:40 2008
