9BXB
CRYSTAL STRUCTURE OF HIV-1 LM/HS CLADE A/E CRF01 GP120 CORE IN COMPLEX WITH DL-III-14
This is a non-PDB format compatible entry.
Summary for 9BXB
| Entry DOI | 10.2210/pdb9bxb/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 |
| Biological source | Human immunodeficiency virus 1 |
| Total number of polymer chains | 1 |
| Total formula weight | 42258.90 |
| Authors | |
| Primary citation | Lee, D.,Niu, L.,Ding, S.,Zhu, H.,Tolbert, W.D.,Medjahed, H.,Beaudoin-Bussieres, G.,Abrams, C.,Finzi, A.,Pazgier, M.,Smith 3rd, A.B. Optimization of a Piperidine CD4-Mimetic Scaffold Sensitizing HIV-1 Infected Cells to Antibody-Dependent Cellular Cytotoxicity. Acs Med.Chem.Lett., 15:1961-1969, 2024 Cited by PubMed Abstract: The ability of the HIV-1 accessory proteins Nef and Vpu to decrease CD4 protects infected cells from antibody-dependent cellular cytotoxicity (ADCC) by limiting the exposure of vulnerable epitopes to envelope glycoprotein (Env). Small-molecule CD4 mimetics (CD4mcs) based on piperidine scaffolds represent a new family of agents capable of sensitizing HIV-1-infected cells to ADCC by exposing CD4-induced (CD4i) epitopes on Env that are recognized by non-neutralizing antibodies which are abundant in plasma of people living with HIV. Here, we employed the combined methods of parallel synthesis, structure-based design, and optimization to generate a new line of piperidine-based CD4mcs, which sensitize HIV-1 infected cells to ADCC activity. The X-ray crystallographic study of the CD4mcs within the gp120 residues suggests that the positioning of the CD4mc inside the Phe43 cavity and synergistic contact of the CD4mc with the β loop and the α-helix lead to improved antiviral activity. PubMed: 39563795DOI: 10.1021/acsmedchemlett.4c00403 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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