2hxm
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(New page: 200px<br /> <applet load="2hxm" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hxm, resolution 1.30Å" /> '''Complex of UNG2 and...)
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Revision as of 20:31, 12 November 2007
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Complex of UNG2 and a small Molecule synthetic Inhibitor
Contents |
Overview
Human nuclear uracil DNA glycosylase (UNG2) is a cellular DNA repair, enzyme that is essential for a number of diverse biological phenomena, ranging from antibody diversification to B-cell lymphomas and type-1 human, immunodeficiency virus infectivity. During each of these processes, UNG2, recognizes uracilated DNA and excises the uracil base by flipping it into, the enzyme active site. We have taken advantage of the extrahelical uracil, recognition mechanism to build large small-molecule libraries in which, uracil is tethered via flexible alkane linkers to a collection of, secondary binding elements. This high-throughput synthesis and screening, approach produced two novel uracil-tethered inhibitors of UNG2, the best, of which was crystallized with the enzyme. Remarkably, this inhibitor, mimics the crucial hydrogen bonding and electrostatic interactions, previously observed in UNG2 complexes with damaged uracilated DNA. Thus, the environment of the binding site selects for library ligands that share, these DNA features. This is a general approach to rapid discovery of, inhibitors of enzymes that recognize extrahelical damaged bases.
Disease
Known diseases associated with this structure: Immunodeficiency with hyper IgM, type 4 OMIM:[191525]
About this Structure
2HXM is a Single protein structure of sequence from Homo sapiens with 302 as ligand. Full crystallographic information is available from OCA.
Reference
Mimicking damaged DNA with a small molecule inhibitor of human UNG2., Krosky DJ, Bianchet MA, Seiple L, Chung S, Amzel LM, Stivers JT, Nucleic Acids Res. 2006;34(20):5872-9. Epub 2006 Oct 24. PMID:17062624
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