6K3J

Solution structure of APOBEC3G-CD2 with ssDNA, Product A

Summary for 6K3J

• Entry DOI: 10.2210/pdb6k3j/pdb
• Descriptor: DNA dC->dU-editing enzyme APOBEC-3G, DNA (5'-D(*AP*TP*TP*CP*UP*(IUR)P*AP*AP*TP*T)-3'), ZINC ION (3 entities in total)
• Functional Keywords: apobec3g, dna cytidine deaminase complex with dna, hydrolase-dna complex, hydrolase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 25334.24

Authors

Cao, C.,Yan, X.,Lan, W.,Wang, C. (deposition date: 2019-05-19, release date: 2019-06-12, Last modification date: 2024-05-15)

Primary citation

Yan, X.,Lan, W.,Wang, C.,Cao, C.
Structural Investigations on the Interactions between Cytidine Deaminase Human APOBEC3G and DNA.
Chem Asian J, 14:2235-2241, 2019

PubMed Abstract: Human APOBEC3G (A3G) inhibits the replication of human immunodeficiency virus-1 by deaminating cytidine at the 3'-end in the target motif 5'-CCC-3' in viral cDNA during reverse transcription. It in vitro deaminates two consecutive cytidines in a 3'->5' order. Although a crystal structure of the A3G catalytic domain (A3G-CD2) with DNA was reported, it is unknown why residues involved in enzymatic reaction are distributed widely. Here, we introduced an iodine atom into the C-5 position of cytidine (dC ) in DNA 5'-ATTC C C A ATT-3' (TCCC ). It switches the deamination sequence preference from CCC to TCC, although small dC deamination was observed. Solution structures of A3G-CD2 in complexes with products DNA TCUC and TCUU indicate that the substrate DNA binds A3G-CD2 in TCC and CCC modes. The dC deamination correlates with the 4 base type. The CCC mode favours dC deamination, while the TCC mode results in dC deamination. These studies present an extensive basis to design inhibitors to impede viral evolvability.

PubMed: 31116511
DOI: 10.1002/asia.201900480

Experimental method

SOLUTION NMR