3fcl

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
{{STRUCTURE_3fcl| PDB=3fcl | SCENE= }}
+
==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]] 1.70&Aring;' scene=''>
-
{{ABSTRACT_PUBMED_19396178}}
+
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[3fcl]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FCL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FCL FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3FL:3-{[(4-{[(2,6-DIOXO-1,2,3,6-TETRAHYDROPYRIMIDIN-4-YL)METHYL]AMINO}BUTYL)AMINO]METHYL}BENZOIC+ACID'>3FL</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></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 Homo sapiens])</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://www.rcsb.org/pdb/explore.do?structureId=3fcl RCSB], [http://www.ebi.ac.uk/pdbsum/3fcl PDBsum]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[[http://www.uniprot.org/uniprot/UNG_HUMAN UNG_HUMAN]] Defects in UNG are a cause of immunodeficiency with hyper-IgM type 5 (HIGM5) [MIM:[http://omim.org/entry/608106 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.<ref>PMID:12958596</ref> <ref>PMID:15967827</ref>
 +
== Function ==
 +
[[http://www.uniprot.org/uniprot/UNG_HUMAN 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 ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fc/3fcl_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
The 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.
-
==Disease==
+
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<ref>PMID:19396178</ref>
-
[[http://www.uniprot.org/uniprot/UNG_HUMAN UNG_HUMAN]] Defects in UNG are a cause of immunodeficiency with hyper-IgM type 5 (HIGM5) [MIM:[http://omim.org/entry/608106 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.<ref>PMID:12958596</ref><ref>PMID:15967827</ref>
+
-
==Function==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[http://www.uniprot.org/uniprot/UNG_HUMAN 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.
+
</div>
-
 
+
-
==About this Structure==
+
-
[[3fcl]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FCL OCA].
+
==See Also==
==See Also==
-
*[[DNA glycosylate|DNA glycosylate]]
+
*[[DNA glycosylase|DNA glycosylase]]
-
 
+
*[[Uracil-DNA glycosylase|Uracil-DNA glycosylase]]
-
==Reference==
+
== References ==
-
<ref group="xtra">PMID:019396178</ref><references group="xtra"/><references/>
+
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Amzel, L M.]]
+
[[Category: Amzel, L M]]
-
[[Category: Bianchet, M A.]]
+
[[Category: Bianchet, M A]]
-
[[Category: Chung, S.]]
+
[[Category: Chung, S]]
-
[[Category: Parker, J B.]]
+
[[Category: Parker, J B]]
-
[[Category: Stivers, J T.]]
+
[[Category: Stivers, J T]]
[[Category: Disease mutation]]
[[Category: Disease mutation]]
[[Category: Dna damage]]
[[Category: Dna damage]]

Revision as of 14:43, 5 January 2015

Complex of UNG2 and a fragment-based designed inhibitor

3fcl, resolution 1.70Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools