8gd5

Crystal Structure of HIV-1 LM/HT Clade A/E CRF01 GP120 Core in Complex with DL-I-102

spinqualitylabelsall models 8gd5, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8gd5 is a 1 chain structure with sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: EPE, NAG, Z2O Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0M3KKW9_9HIV1 Publication Abstract from PubMed 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 (S)-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, (S)-MCG-IV-210 derivatives, based on the piperidine scaffold which engages the gp120 within the Phe43 cavity by targeting the highly conserved Asp(368) 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 alpha-carboxylic acid group of Asp(368), 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. Piperidine CD4-Mimetic Compounds Expose Vulnerable Env Epitopes Sensitizing HIV-1-Infected Cells to ADCC.,Ding S, Tolbert WD, 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 AB 3rd, Finzi A Viruses. 2023 May 17;15(5):1185. doi: 10.3390/v15051185. PMID:37243271 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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