6v3k

Structure of HIV cleaved synaptic complex (CSC) intasome bound with magnesium and INSTI XZ419 (compound 4c)

Loading... Status: waiting for Mol* initialization Structural highlights 6v3k is a 6 chain structure with sequence from [1] and 9hiv1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, QUW, ZN Gene: sso7d, sso7d-1, SSO10610 (9HIV1) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DN7D_SACS2] Can constrain negative DNA supercoils. May be involved in maintaining the integrity of the genome at high temperature (By similarity). Stimulates the Holliday junction cleavage activity of Hjc (PubMed:11709558).[UniProtKB:P61990] Publication Abstract from PubMed The HIV intasome is a large nucleoprotein assembly that mediates the integration of a DNA copy of the viral genome into host chromatin. Intasomes are targeted by the latest generation of antiretrovirals, integrase (IN) strand transfer inhibitors (INSTIs). Challenges associated with lentiviral intasome biochemistry have hindered high-resolution structural studies of how INSTIs bind to their native drug target. Here, we present high-resolution cryo-electron microscopy (cryo-EM) structures of HIV intasomes bound to the latest generation INSTIs. These structures highlight how small changes in the IN active site can have significant implications for drug binding and design and provide mechanistic insights into why a leading INSTI retains efficacy against a broad spectrum of drug resistant variants. The data have implications for expanding effective treatments available for HIV-infected individuals. Structural basis for strand transfer inhibitor binding to HIV intasomes.,Passos DO, Li M, Jozwik IK, Zhao XZ, Santos-Martins D, Yang R, Smith SJ, Jeon Y, Forli S, Hughes SH, Burke TR Jr, Craigie R, Lyumkis D Science. 2020 Jan 30. pii: science.aay8015. doi: 10.1126/science.aay8015. PMID:32001521 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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