8fa0 | pdb_00008fa0

Crystal structure of clade A/E 93TH057 HIV-1 gp120 core in complex with NBD-14208, an HIV-1 gp120 antagonist

spinqualitylabelsall models 8fa0, resolution 2.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8fa0 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.09Å Ligands: EPE, NAG, XKR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0M3KKW8_HUMAN Publication Abstract from PubMed As part of our effort to discover drugs that target HIV-1 entry, we report the antiviral activity and crystal structures of two novel inhibitors in a complex with a gp120 core. NBD-14204 showed similar antiviral activity against all the clinical isolates tested. The IC(50) values were in the range of 0.24-0.9 microM with an overall mean of 0.47 +/- 0.03 microM, showing slightly better activity against the clinical isolates than against the lab-adapted HIV-1(HXB2) (IC(50) = 0.96 +/- 0.1 microM)(.) Moreover, the antiviral activity of NBD-14208 was less consistent, showing a wider range of IC(50) values (0.66-5.7 microM) with an overall mean of 3 +/- 0.25 microM and better activity against subtypes B and D (Mean IC(50) 2.2-2.5 microM) than the A, C and Rec viruses (Mean IC(50) 2.9-3.9 microM). SI of NBD-14204 was about 10-fold higher than NBD-14208, making it a better lead compound for further optimization. In addition, we tested these compounds against S375Y and S375H mutants of gp120, which occurred in some clades and observed these to be sensitive to NBD-14204 and NBD-14208. These inhibitors also showed modest activity against HIV-1 reverse transcriptase. Furthermore, we determined the crystal structures of both inhibitors in complexes with gp120 cores. As expected, both NBD-14204 and NBD-14208 bind primarily within the Phe43 cavity. It is noteworthy that the electron density of the thiazole ring in both structures was poorly defined due to the flexibility of this scaffold, suggesting that these compounds maintain substantial entropy, even when bound to the Phe43 cavity. Antiviral Activity and Crystal Structures of HIV-1 gp120 Antagonists.,Curreli F, Kwon YD, Nicolau I, Burgos G, Altieri A, Kurkin AV, Verardi R, Kwong PD, Debnath AK Int J Mol Sci. 2022 Dec 15;23(24):15999. doi: 10.3390/ijms232415999. PMID:36555641 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Gp120 3D structures

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