3F4Z
Trimeric helix bundle formed by an alpha/beta-peptide derivative of the HIV gp41 CHR domain
Summary for 3F4Z
| Entry DOI | 10.2210/pdb3f4z/pdb |
| Related | 3F4Y 3F50 |
| Descriptor | alpha/beta-peptide analogue of the HIV gp41 CHR domain, (4S)-2-METHYL-2,4-PENTANEDIOL (3 entities in total) |
| Functional Keywords | alpha/beta-peptide, helix bundle, viral protein |
| Total number of polymer chains | 3 |
| Total formula weight | 14523.65 |
| Authors | Horne, W.S.,Gellman, S.H. (deposition date: 2008-11-03, release date: 2009-09-15, Last modification date: 2023-11-15) |
| Primary citation | Horne, W.S.,Johnson, L.M.,Ketas, T.J.,Klasse, P.J.,Lu, M.,Moore, J.P.,Gellman, S.H. Structural and biological mimicry of protein surface recognition by alpha/beta-peptide foldamers Proc.Natl.Acad.Sci.USA, 106:14751-14756, 2009 Cited by PubMed Abstract: Unnatural oligomers that can mimic protein surfaces offer a potentially useful strategy for blocking biomedically important protein-protein interactions. Here we evaluate an approach based on combining alpha- and beta-amino acid residues in the context of a polypeptide sequence from the HIV protein gp41, which represents an excellent testbed because of the wealth of available structural and biological information. We show that alpha/beta-peptides can mimic structural and functional properties of a critical gp41 subunit. Physical studies in solution, crystallographic data, and results from cell-fusion and virus-infectivity assays collectively indicate that the gp41-mimetic alpha/beta-peptides effectively block HIV-cell fusion via a mechanism comparable to that of gp41-derived alpha-peptides. An optimized alpha/beta-peptide is far less susceptible to proteolytic degradation than is an analogous alpha-peptide. Our findings show how a two-stage design approach, in which sequence-based alpha-->beta replacements are followed by site-specific backbone rigidification, can lead to physical and biological mimicry of a natural biorecognition process. PubMed: 19706443DOI: 10.1073/pnas.0902663106 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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