8GD5
Crystal Structure of HIV-1 LM/HT Clade A/E CRF01 GP120 Core in Complex with DL-I-102
Summary for 8GD5
| Entry DOI | 10.2210/pdb8gd5/pdb |
| Descriptor | HIV-1 LM/HS clade A/E CRF01 gp120 core, 2-acetamido-2-deoxy-beta-D-glucopyranose, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (5 entities in total) |
| Functional Keywords | hiv-1 gp120, clade a/e cf01, viral protein-inhibitor complex, viral protein/inhibitor |
| Biological source | Human immunodeficiency virus 1 |
| Total number of polymer chains | 1 |
| Total formula weight | 42360.00 |
| Authors | Tolbert, W.D.,Nguyen, D.N.,Pazgier, M. (deposition date: 2023-03-03, release date: 2023-06-07, Last modification date: 2024-11-20) |
| Primary citation | Ding, S.,Tolbert, W.D.,Zhu, H.,Lee, D.,Marchitto, L.,Higgins, T.,Zhao, X.,Nguyen, D.,Sherburn, R.,Richard, J.,Gendron-Lepage, G.,Medjahed, H.,Mohammadi, M.,Abrams, C.,Pazgier, M.,Smith III, A.B.,Finzi, A. Piperidine CD4-Mimetic Compounds Expose Vulnerable Env Epitopes Sensitizing HIV-1-Infected Cells to ADCC. Viruses, 15:-, 2023 Cited by PubMed Abstract: The ability of the HIV-1 accessory proteins Nef and Vpu to decrease CD4 levels contributes to the protection of infected cells from antibody-dependent cellular cytotoxicity (ADCC) by preventing the exposure of Env vulnerable epitopes. Small-molecule CD4 mimetics (CD4mc) based on the indane and piperidine scaffolds such as (+)-BNM-III-170 and ()-MCG-IV-210 sensitize HIV-1-infected cells to ADCC by exposing CD4-induced (CD4i) epitopes recognized by non-neutralizing antibodies that are abundantly present in plasma from people living with HIV. Here, we characterize a new family of CD4mc, ()-MCG-IV-210 derivatives, based on the piperidine scaffold which engages the gp120 within the Phe43 cavity by targeting the highly conserved Asp Env residue. We utilized structure-based approaches and developed a series of piperidine analogs with improved activity to inhibit the infection of difficult-to-neutralize tier-2 viruses and sensitize infected cells to ADCC mediated by HIV+ plasma. Moreover, the new analogs formed an H-bond with the α-carboxylic acid group of Asp, opening a new avenue to enlarge the breadth of this family of anti-Env small molecules. Overall, the new structural and biological attributes of these molecules make them good candidates for strategies aimed at the elimination of HIV-1-infected cells. PubMed: 37243271DOI: 10.3390/v15051185 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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