Summary information and primary citation
- PDB-id
- 6k3k; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- hydrolase-DNA
- Method
- NMR
- Summary
- Solution structure of apobec3g-cd2 with ssDNA, product b
- Reference
- Yan X, Lan W, Wang C, Cao C (2019): "Structural Investigations on the Interactions between Cytidine Deaminase Human APOBEC3G and DNA." Chem Asian J, 14, 2235-2241. doi: 10.1002/asia.201900480.
- Abstract
- 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.
