4DZU

Complex of 3-alpha bound to gp41-5

Summary for 4DZU

• Entry DOI: 10.2210/pdb4dzu/pdb
• Related: 3o42 4DZV
• Descriptor: gp41-5, 3-alpha, GLYCEROL, ... (4 entities in total)
• Functional Keywords: viral fusion, de novo protein
• Biological source: Synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 27104.18

Authors

Johnson, L.M.,Mortenson, D.E.,Yun, H.G.,Horne, W.S.,Ketas, T.J.,Lu, M.,Moore, J.P.,Gellman, S.H. (deposition date: 2012-03-01, release date: 2012-05-02, Last modification date: 2024-02-28)

Primary citation

Johnson, L.M.,Mortenson, D.E.,Yun, H.G.,Horne, W.S.,Ketas, T.J.,Lu, M.,Moore, J.P.,Gellman, S.H.
Enhancement of alpha-helix mimicry by an alpha / beta-peptide foldamer via incorporation of a dense ionic side-chain array.
J.Am.Chem.Soc., 134:7317-7320, 2012

PubMed Abstract: We report a new method for preorganization of α/β-peptide helices, based on the use of a dense array of acidic and basic side chains. Previously we have used cyclically constrained β residues to promote α/β-peptide helicity; here we show that an engineered ion pair array can be comparably effective, as indicated by mimicry of the CHR domain of HIV protein gp41. The new design is effective in biochemical and cell-based infectivity assays; however, the resulting α/β-peptide is susceptible to proteolysis. This susceptibility was addressed via introduction of a few cyclic β residues near the cleavage site, to produce the most stable, effective α/β-peptide gp41 CHR analogue identified. Crystal structures of an α- and α/β-peptide (each involved in a gp41-mimetic helix bundle) that contain the dense acid/base residue array manifest disorder in the ionic side chains, but there is little side-chain disorder in analogous α- and α/β-peptide structures with a sparser ionic side-chain array. These observations suggest that dense arrays of complementary acidic and basic residues can provide conformational stabilization via Coulombic attractions that do not require entropically costly ordering of side chains.

PubMed: 22524614
DOI: 10.1021/ja302428d

Experimental method

X-RAY DIFFRACTION (2.1 Å)