Structural highlights
Function
[UNG_VACCC] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine. Also part of a heterodimeric processivity factor which potentiates the DNA polymerase activity. Binds to DNA (By similarity). [A20_VACCC] Plays an essential role in viral DNA replication by acting as the polymerase processivity factor together with protein D4. May serve as a bridge which links the DNA polymerase E9 and the uracil DNA glycosylase (By similarity).
Publication Abstract from PubMed
The Vaccinia virus polymerase holoenzyme is composed of three subunits: E9, the catalytic DNA polymerase subunit; D4, a uracil-DNA glycosylase; and A20, a protein with no known enzymatic activity. The D4/A20 heterodimer is the DNA polymerase cofactor, the function of which is essential for processive DNA synthesis. The recent crystal structure of D4 bound to the first 50 amino acids of A20 (D4/A201-50) revealed the importance of three residues, forming a cation-pi interaction at the dimerization interface, for complex formation. These are Arg167 and Pro173 of D4 and Trp43 of A20. Here, the crystal structures of the three mutants D4-R167A/A201-50, D4-P173G/A201-50 and D4/A201-50-W43A are presented. The D4/A20 interface of the three structures has been analysed for atomic solvation parameters and cation-pi interactions. This study confirms previous biochemical data and also points out the importance for stability of the restrained conformational space of Pro173. Moreover, these new structures will be useful for the design and rational improvement of known molecules targeting the D4/A20 interface.
Structural analysis of point mutations at the Vaccinia virus A20/D4 interface.,Contesto-Richefeu C, Tarbouriech N, Brazzolotto X, Burmeister WP, Peyrefitte CN, Iseni F Acta Crystallogr F Struct Biol Commun. 2016 Sep;72(Pt 9):687-91. doi:, 10.1107/S2053230X16011778. Epub 2016 Aug 9. PMID:27599859[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Contesto-Richefeu C, Tarbouriech N, Brazzolotto X, Burmeister WP, Peyrefitte CN, Iseni F. Structural analysis of point mutations at the Vaccinia virus A20/D4 interface. Acta Crystallogr F Struct Biol Commun. 2016 Sep;72(Pt 9):687-91. doi:, 10.1107/S2053230X16011778. Epub 2016 Aug 9. PMID:27599859 doi:http://dx.doi.org/10.1107/S2053230X16011778
