4ygm

Vaccinia virus his-D4/A20(1-50) in complex with uracil

spinqualitylabelsall models 4ygm, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ygm is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4, URA Related: 4od8 Activity: Uracil-DNA glycosylase, with EC number 3.2.2.27 Resources: FirstGlance, OCA, RCSB, PDBsum 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 Vaccinia virus polymerase holoenzyme is composed of the DNA polymerase catalytic subunit E9 associated with its heterodimeric co-factor A20/D4 required for processive genome synthesis. While A20 has no known enzymatic activity, D4 is an active uracil-DNA glycosylase (UNG) . The presence of a repair enzyme as a component of the viral replication machinery suggest that, for poxviruses, DNA synthesis and base excision repair is coupled. We present the 2.7A crystal structure of the complex formed by D4 and the first 50 amino acids of A20 (D4/A201 50) bound to a 10-mer DNA duplex containing an abasic site resulting from the cleavage of a uracil base. Comparison of the viral complex with its human counterpart revealed major divergences in the contacts between protein and DNA and in the enzyme orientation on the DNA. However, the conformation of the dsDNA within both structures is very similar suggesting a dominant role of the DNA conformation for UNG function. In contrast to human UNG, D4 appears rigid and we do not observe a conformational change upon DNA binding. We also studied the interaction of D4/A201-50 with different DNA oligomers by surface plasmon resonance. D4 binds weakly to non-specific DNA and to uracil containing substrates but binds abasic sites with a Kd < 1.4 muM. This second DNA complex structure of a family I UNG gives new insight into the role of D4 as a co-factor of vaccinia virus DNA polymerase and allows a better understanding of the structural determinants required for UNG action. Crystal Structure of the Vaccinia Virus Uracil-DNA Glycosylase in Complex with DNA.,Burmeister WP, Tarbouriech N, Fender P, Contesto-Richefeu C, Peyrefitte CN, Iseni F J Biol Chem. 2015 Jun 4. pii: jbc.M115.648352. PMID:26045555 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Uracil-DNA glycosylase

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