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Structural Investigations on the Interactions between Cytidine Deaminase Human APOBEC3G and DNA
Author(s) -
Yan Xiaoxuan,
Lan Wenxian,
Wang Chunxi,
Cao Chunyang
Publication year - 2019
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201900480
Subject(s) - deamination , cytidine deaminase , cytidine , apobec3g , activation induced (cytidine) deaminase , dna , reverse transcriptase , cytosine , chemistry , biology , microbiology and biotechnology , biochemistry , enzyme , genetics , polymerase chain reaction , somatic hypermutation , antibody , gene , b cell
Human APOBEC3G (A3G) inhibits the replication of human immunodeficiency virus‐1 by deaminating cytidine at the 3′‐end in the target motif 5′‐CC C ‐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 6 I ) in DNA 5′‐ATTC 4 C 5 C 6 I A 7 ATT‐3′ (TCCC 6 I ). It switches the deamination sequence preference from CCC to TCC, although small dC 6 I deamination was observed. Solution structures of A3G‐CD2 in complexes with products DNA TCUC 6 I and TCUU 6 I indicate that the substrate DNA binds A3G‐CD2 in TCC and CCC modes. The dC 6 deamination correlates with the 4 th base type. The CCC mode favours dC 6 deamination, while the TCC mode results in dC 5 deamination. These studies present an extensive basis to design inhibitors to impede viral evolvability.