PDBsum entry 5cn0

Viral protein

PDB id: 5cn0

Contents

Protein chain

70 a.a.

Ligands

PEG ×2

Metals

_MG

Waters ×57

PDB id:

5cn0

Name:

Viral protein

Title:

Artificial HIV fusion inhibitor ap2 fused to thE C-terminus of gp41 nhr

Structure:

Envelope glycoprotein,ap2. Chain: a. Fragment: c-terminus (unp residues 35-70). Synonym: gp41. Engineered: yes. Other_details: the fusion protein of expression tag, c-terminus residues 35-70 from gp4 and artificial inhibitor ap1

Source:

Human immunodeficiency virus 1, synthetic construct. Hiv1. Organism_taxid: 11676, 32630. Gene: env. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.90Å R-factor: 0.200 R-free: 0.232

Authors:

Y.Zhu,S.Ye,R.Zhang

Key ref:

X.Zhu et al. (2015). Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy. Sci Rep, 5, 13028. PubMed id: 26286358 DOI: 10.1038/srep13028

Date:

17-Jul-15 Release date: 16-Sep-15

Protein chain

P04578  (ENV_HV1H2) -  Envelope glycoprotein gp160 from Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)

Seq: 856 a.a.

Struc: 70 a.a.*

* PDB and UniProt seqs differ at 33 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/srep13028

Sci Rep 5:13028 (2015)

PubMed id: 26286358

Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy.

X.Zhu, Y.Zhu, S.Ye, Q.Wang, W.Xu, S.Su, Z.Sun, F.Yu, Q.Liu, C.Wang, T.Zhang, Z.Zhang, X.Zhang, J.Xu, L.Du, K.Liu, L.Lu, R.Zhang, S.Jiang.

ABSTRACT

Enfuvirtide (T20), is the first HIV fusion inhibitor approved for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, its clinical application is limited because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients. Using an artificial peptide strategy, we designed a peptide with non-native protein sequence, AP3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20. While the preexisting antibodies in HIV-infected patients significantly suppressed T20's antiviral activity, these antibodies neither recognized AP3, nor attenuated its anti-HIV-1 activity. Structurally different from T20, AP3 could fold into single-helix and interact with gp41 NHR. The two residues, Met and Thr, at the N-terminus of AP3 form a hook-like structure to stabilize interaction between AP3 and NHR helices. Therefore, AP3 has potential for further development as a new HIV fusion inhibitor with improved antiviral efficacy, resistance profile and pharmacological properties over enfuvirtide. Meanwhile, this study highlighted the advantages of artificially designed peptides, and confirmed that this strategy could be used in developing artificial peptide-based viral fusion inhibitors against HIV and other enveloped viruses.