3fcl: Difference between revisions
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==Complex of UNG2 and a fragment-based designed inhibitor== | ==Complex of UNG2 and a fragment-based designed inhibitor== | ||
<StructureSection load='3fcl' size='340' side='right' caption='[[3fcl]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='3fcl' size='340' side='right' caption='[[3fcl]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fcf|3fcf]], [[3fci|3fci]], [[3fck|3fck]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fcf|3fcf]], [[3fci|3fci]], [[3fck|3fck]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UNG, DGU, UNG1, UNG15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UNG, DGU, UNG1, UNG15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3fcl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fcl OCA], [http://pdbe.org/3fcl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fcl RCSB], [http://www.ebi.ac.uk/pdbsum/3fcl PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3fcl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fcl OCA], [http://pdbe.org/3fcl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fcl RCSB], [http://www.ebi.ac.uk/pdbsum/3fcl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fcl ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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</div> | </div> | ||
<div class="pdbe-citations 3fcl" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3fcl" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Parker, J B]] | [[Category: Parker, J B]] | ||
[[Category: Stivers, J T]] | [[Category: Stivers, J T]] | ||
[[Category: Alternative splicing]] | |||
[[Category: Disease mutation]] | [[Category: Disease mutation]] | ||
[[Category: Dna damage]] | [[Category: Dna damage]] | ||
Revision as of 09:38, 1 November 2017
Complex of UNG2 and a fragment-based designed inhibitorComplex of UNG2 and a fragment-based designed inhibitor
Structural highlights
Disease[UNG_HUMAN] Defects in UNG are a cause of immunodeficiency with hyper-IgM type 5 (HIGM5) [MIM:608106]. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.[1] [2] Function[UNG_HUMAN] 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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe linking together of molecular fragments that bind to adjacent sites on an enzyme can lead to high-affinity inhibitors. Ideally, this strategy would use linkers that do not perturb the optimal binding geometries of the fragments and do not have excessive conformational flexibility that would increase the entropic penalty of binding. In reality, these aims are seldom realized owing to limitations in linker chemistry. Here we systematically explore the energetic and structural effects of rigid and flexible linkers on the binding of a fragment-based inhibitor of human uracil DNA glycosylase. Analysis of the free energies of binding in combination with cocrystal structures shows that the flexibility and strain of a given linker can have a substantial impact on binding affinity even when the binding fragments are optimally positioned. Such effects are not apparent from inspection of structures and underscore the importance of linker optimization in fragment-based drug discovery efforts. Impact of linker strain and flexibility in the design of a fragment-based inhibitor.,Chung S, Parker JB, Bianchet M, Amzel LM, Stivers JT Nat Chem Biol. 2009 Jun;5(6):407-13. Epub 2009 Apr 26. PMID:19396178[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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