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3VU5

Short peptide HIV entry Inhibitor SC22EK

Summary for 3VU5
Entry DOI10.2210/pdb3vu5/pdb
Related1env 3VU6 3vgx
DescriptorTransmembrane protein gp41, SC22, SULFATE ION, ... (5 entities in total)
Functional Keywords6-helix bundle, coiled-coil, membrane, fusion inhibitor, hiv entry, membrane protein-inhibitor complex, membrane protein/inhibitor
Biological sourceHuman immunodeficiency virus 1 (HIV-1)
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Cellular locationTransmembrane protein gp41: Virion membrane; Single-pass type I membrane protein. Surface protein gp120: Virion membrane; Peripheral membrane protein: P03375
Total number of polymer chains2
Total formula weight7488.66
Authors
Yao, X.,Chong, H.H.,Waltersperger, S.,Wang, M.T.,He, Y.X.,Cui, S. (deposition date: 2012-06-19, release date: 2012-12-19, Last modification date: 2024-11-06)
Primary citationChong, H.H.,Yao, X.,Qiu, Z.,Sun, J.,Zhang, M.,Waltersperger, S.,Wang, M.T.,Liu, S.-L.,Cui, S.,He, Y.X.
Short-peptide fusion inhibitors with high potency against wild-type and enfuvirtide-resistant HIV-1
Faseb J., 27:1203-1213, 2013
Cited by
PubMed Abstract: Peptides derived from the C-terminal heptad repeat (C peptides) of HIV-1 gp41 are potent inhibitors against virus entry. However, development of a short C peptide possessing high anti-HIV potency is considered a daunting challenge. We recently discovered that the residues Met626 and Thr627 preceding the pocket-binding domain of the C peptide adopt a unique M-T hook structure that is crucial for the design of HIV-1 fusion inhibitors. In this study, we first presented a proof-of-concept prototype that the M-T hook residues can dramatically improve the antiviral activity and thermostability of a short C peptide. We then generated a 24-mer peptide termed MT-SC22EK by incorporating the M-T hook structure to the N terminus of the poorly active short C peptide SC22EK. Amazingly, MT-SC22EK inhibited HIV-1-mediated cell fusion and infection at a level comparable to C34, T1249, SC29EK, and sifuvirtide, and it was highly active against diverse HIV-1 subtypes and variants, including those T20 (enfuvirtide) and SC29EK-resistant viruses. The high-resolution crystal structure of MT-SC22EK reveals the N-terminal M-T hook conformation folded by incorporated Met626 and Thr627 and identifies the C-terminal boundary critical for the anti-HIV activity. Collectively, our studies provide new insights into the mechanisms of HIV-1 fusion and its inhibition.
PubMed: 23233535
DOI: 10.1096/fj.12-222547
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.087 Å)
Structure validation

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