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2015 ; 471
(1
): 25-35
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gab.com Text
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English Wikipedia
DNA cytosine and methylcytosine deamination by APOBEC3B: enhancing methylcytosine
deamination by engineering APOBEC3B
#MMPMID26195824
Fu Y
; Ito F
; Zhang G
; Fernandez B
; Yang H
; Chen XS
Biochem J
2015[Oct]; 471
(1
): 25-35
PMID26195824
show ga
APOBEC (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like) is a
family of enzymes that deaminates cytosine (C) to uracil (U) on nucleic acid.
APOBEC3B (A3B) functions in innate immunity against intrinsic and invading
retroelements and viruses. A3B can also induce genomic DNA mutations to cause
cancer. A3B contains two cytosine deaminase domains (CD1, CD2), and there are
conflicting reports about whether both domains are active. Here we demonstrate
that only CD2 of A3B (A3BCD2) has C deamination activity. We also reveal that
both A3B and A3BCD2 can deaminate methylcytosine (mC). Guided by structural and
functional analysis, we successfully engineered A3BCD2 to gain over two orders of
magnitude higher activity for mC deamination. Important determinants that
contribute to the activity and selectivity for mC deamination have been
identified, which reveals that multiple elements, rather than single ones,
contribute to the mC deamination activity and selectivity in A3BCD2 and possibly
other APOBECs.