6k3j

Solution structure of APOBEC3G-CD2 with ssDNA, Product A

spinqualitylabelsall models 6k3j Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6k3j is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, models Ligands: 5IU, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ABC3G_HUMAN DNA deaminase (cytidine deaminase) that mediates a form of innate resistance to retroviral infections (at least to HIV-1 infection) by triggering G-to-A hypermutation in the newly synthesized viral DNA. The replacements C-to-U in the minus strand DNA of HIV-1 during reverse transcription, leads to G-to-A transitions in the plus strand. The inhibition of viral replication is either due to the degradation of the minus strand before its integration or to the lethality of the hypermutations. Modification of both DNA strands is not excluded. This antiviral activity is neutralized by the virion infectivity factor (VIF), that prevents the incorporation of APOBEC3G into progeny HIV-1 virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome. May also prevent the transposition of a subset of retroelements. Binds a variety of RNAs, but does not display detectable APOB, NF1 and NAT1 mRNA editing. Publication Abstract from PubMed Human APOBEC3G (A3G) is a cytidine deaminase, which inhibits the replication of human immunodeficiency virus-1 by deaminating cytidine at 3'-end in target motif 5'-CCCA-3' in viral cDNA during the reverse transcription. It can in vitro deaminate two consecutive cytidines in a 3'->5' order. Although the crystal structure of A3G catalytic domain (A3G-CD2) variant with DNA was reported, it's still unknown why the residues involved in DNA binding and enzymatic deamination are distributed widely on its surface. To address this, we introduced steric iodine into C-5 position of cytidine (dC6I) in substrate 5'-ATTC4C5C6IA7ATT-3' DNA (abbreviated as TCCC6I). This modification significantly switches the sequence preference of A3G catalytic deamination from 5'-CCC-3' into 5'-TCC-3', although slight dC6I deamination was observed. Solution structures of A3G-CD2 in complex with deamination products TCUC6I DNA and TCUU6I DNA were resolved, which indicate that substrate DNA interacts with A3G-CD2 in two binding modes (termed as TCC and CCC). The dC6 deamination rate is dependent on the type of the most 5'-end base in the motif 5'-XCCA-3' (X=C,T,A or G). CCC mode is in favour of dC6 deamination, while TCC mode avails dC5 deamination. These studies present extensively structural basis to design inhibitors to impede the evolvability of viruses. Structural Investigations on the Interactions between Cytidine Deaminase Human APOBEC3G and DNA.,Yan X, Lan W, Wang C, Cao C Chem Asian J. 2019 May 22. doi: 10.1002/asia.201900480. PMID:31116511 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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