Crystal structure of SAUGI/HSV UDG complexCrystal structure of SAUGI/HSV UDG complex

Structural highlights

5ays is a 4 chain structure with sequence from Human alphaherpesvirus 1 strain 17 and Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.09Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UNG_HHV11 Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or deamination of cytosine. Therefore may reduce deleterious uracil incorporation into the viral genome, particularly, in terminally differentiated neurons which lack DNA repair enzymes.[1] [2]

Publication Abstract from PubMed

Uracil-DNA glycosylases (UDGs) are highly conserved proteins that can be found in a wide range of organisms, and are involved in the DNA repair and host defense systems. UDG activity is controlled by various cellular factors, including the uracil-DNA glycosylase inhibitors, which are DNA mimic proteins that prevent the DNA binding sites of UDGs from interacting with their DNA substrate. To date, only three uracil-DNA glycosylase inhibitors, phage UGI, p56, and Staphylococcus aureus SAUGI, have been determined. We show here that SAUGI has differential inhibitory effects on UDGs from human, bacteria, Herpes simplex virus (HSV; human herpesvirus 1) and Epstein-Barr virus (EBV; human herpesvirus 4). Newly determined crystal structures of SAUGI/human UDG and a SAUGI/HSVUDG complex were used to explain the differential binding activities of SAUGI on these two UDGs. Structural-based protein engineering was further used to modulate the inhibitory ability of SAUGI on human UDG and HSVUDG. The results of this work extend our understanding of DNA mimics as well as potentially opening the way for novel therapeutic applications for this kind of protein.

Using structural-based protein engineering to modulate the differential inhibition effects of SAUGI on human and HSV uracil DNA glycosylase.,Wang HC, Ho CH, Chou CC, Ko TP, Huang MF, Hsu KC, Wang AH Nucleic Acids Res. 2016 May 19;44(9):4440-9. doi: 10.1093/nar/gkw185. Epub 2016, Mar 14. PMID:26980279[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Savva R, Pearl LH. Nucleotide mimicry in the crystal structure of the uracil-DNA glycosylase-uracil glycosylase inhibitor protein complex. Nat Struct Biol. 1995 Sep;2(9):752-7. PMID:7552746
  2. Krusong K, Carpenter EP, Bellamy SR, Savva R, Baldwin GS. A comparative study of uracil-DNA glycosylases from human and herpes simplex virus type 1. J Biol Chem. 2006 Feb 24;281(8):4983-92. Epub 2005 Nov 22. PMID:16306042 doi:http://dx.doi.org/10.1074/jbc.M509137200
  3. Wang HC, Ho CH, Chou CC, Ko TP, Huang MF, Hsu KC, Wang AH. Using structural-based protein engineering to modulate the differential inhibition effects of SAUGI on human and HSV uracil DNA glycosylase. Nucleic Acids Res. 2016 May 19;44(9):4440-9. doi: 10.1093/nar/gkw185. Epub 2016, Mar 14. PMID:26980279 doi:http://dx.doi.org/10.1093/nar/gkw185

5ays, resolution 2.09Å

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