title: Identification of a single amino acid required for APOBEC3 antiretroviral cytidine deaminase activity.
abstract: During studies of APOBEC3 (A3) anti-human immunodeficiency virus type 1 (anti-HIV-1) mechanisms, we identified a single cysteine at position 320 (C320) that disrupts A3DE activity. This residue is located in the recently identified DNA binding domain in A3G. Replacing C320 with a corresponding tyrosine from A3F (Y307) increased A3DE antiviral activity more than 20-fold. Conversely, replacing A3F Y307 with a cysteine or inserting a similar cysteine into A3B or A3G disrupted the anti-HIV activity of A3. Further investigation uncovered that C320 significantly reduces A3DE catalytic activity.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Dang
authors.forename: Aierken
authors.initials: A
authors.lastname: Abudu
authors.forename: Sungmo
authors.initials: S
authors.lastname: Son
authors.forename: Elena
authors.initials: E
authors.lastname: Harjes
authors.forename: Paul
authors.initials: P
authors.lastname: Spearman
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuo
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Zheng
mesh_terms: D000071478:APOBEC Deaminases; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D003545:Cysteine / Q000235:genetics*; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase; D003545:Cysteine