1ugh: Difference between revisions

Revision as of 11:11, 3 May 2008

CRYSTAL STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE IN COMPLEX WITH A PROTEIN INHIBITOR: PROTEIN MIMICRY OF DNA

OverviewOverview

Uracil-DNA glycosylase inhibitor (Ugi) is a B. subtilis bacteriophage protein that protects the uracil-containing phage DNA by irreversibly inhibiting the key DNA repair enzyme uracil-DNA glycosylase (UDG). The 1.9 A crystal structure of Ugi complexed to human UDG reveals that the Ugi structure, consisting of a twisted five-stranded antiparallel beta sheet and two alpha helices, binds by inserting a beta strand into the conserved DNA-binding groove of the enzyme without contacting the uracil specificity pocket. The resulting interface, which buries over 1200 A2 on Ugi and involves the entire beta sheet and an alpha helix, is polar and contains 22 water molecules. Ugi binds the sequence-conserved DNA-binding groove of UDG via shape and electrostatic complementarity, specific charged hydrogen bonds, and hydrophobic packing enveloping Leu-272 from a protruding UDG loop. The apparent mimicry by Ugi of DNA interactions with UDG provides both a structural mechanism for UDG binding to DNA, including the enzyme-assisted expulsion of uracil from the DNA helix, and a crystallographic basis for the design of inhibitors with scientific and therapeutic applications.

About this StructureAbout this Structure

1UGH is a Protein complex structure of sequences from Bacillus phage pbs2 and Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of human uracil-DNA glycosylase in complex with a protein inhibitor: protein mimicry of DNA., Mol CD, Arvai AS, Sanderson RJ, Slupphaug G, Kavli B, Krokan HE, Mosbaugh DW, Tainer JA, Cell. 1995 Sep 8;82(5):701-8. PMID:7671300 Page seeded by OCA on Sat May 3 11:11:47 2008

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OCA

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 '''CRYSTAL STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE IN COMPLEX WITH A PROTEIN INHIBITOR: PROTEIN MIMICRY OF DNA'''
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 [[Category: Slupphaug, G.]]
 [[Category: Tainer, J A.]]
-[[Category: enzyme-inhibitor complex]]
+[[Category: Enzyme-inhibitor complex]]
-[[Category: glycosylase]]
+[[Category: Glycosylase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 11:11:47 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:09:56 2008''