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4pd2

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Revision as of 17:05, 4 January 2017

Crystal structure of a complex between a C248GH LlFpg mutant and a THF containing DNA

Structural highlights

4pd2 is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	4pcz, 4pdg, 4pdi
Activity:	DNA-formamidopyrimidine glycosylase, with EC number 3.2.2.23
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[FPG_LACLC] Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates.^[1]

Publication Abstract from PubMed

DNA glycosylases from the Fpg/Nei structural superfamily are base excision repair enzymes involved in the removal of a wide variety of mutagen and potentially lethal oxidized purines and pyrimidines. Although involved in genome stability, the recent discovery of synthetic lethal relationships between DNA glycosylases and other pathways highlights the potential of DNA glycosylase inhibitors for future medicinal chemistry development in cancer therapy. By combining biochemical and structural approaches, the physical target of 2-thioxanthine (2TX), an uncompetitive inhibitor of Fpg, was identified. 2TX interacts with the zinc finger (ZnF) DNA binding domain of the enzyme. This explains why the zincless hNEIL1 enzyme is resistant to 2TX. Crystal structures of the enzyme bound to DNA in the presence of 2TX demonstrate that the inhibitor chemically reacts with cysteine thiolates of ZnF and induces the loss of zinc. The molecular mechanism by which 2TX inhibits Fpg may be generalized to all prokaryote and eukaryote ZnF-containing Fpg/Nei-DNA glycosylases. Cell experiments show that 2TX can operate in cellulo on the human Fpg/Nei DNA glycosylases. The atomic elucidation of the determinants for the interaction of 2TX to Fpg provides the foundation for the future design and synthesis of new inhibitors with high efficiency and selectivity.

Zinc finger oxidation of Fpg/Nei DNA glycosylases by 2-thioxanthine: biochemical and X-ray structural characterization.,Biela A, Coste F, Culard F, Guerin M, Goffinont S, Gasteiger K, Ciesla J, Winczura A, Kazimierczuk Z, Gasparutto D, Carell T, Tudek B, Castaing B Nucleic Acids Res. 2014;42(16):10748-61. doi: 10.1093/nar/gku613. Epub 2014 Aug, 20. PMID:25143530^[2]

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

References

↑ Duwat P, de Oliveira R, Ehrlich SD, Boiteux S. Repair of oxidative DNA damage in gram-positive bacteria: the Lactococcus lactis Fpg protein. Microbiology. 1995 Feb;141 ( Pt 2):411-7. PMID:7704272
↑ Biela A, Coste F, Culard F, Guerin M, Goffinont S, Gasteiger K, Ciesla J, Winczura A, Kazimierczuk Z, Gasparutto D, Carell T, Tudek B, Castaing B. Zinc finger oxidation of Fpg/Nei DNA glycosylases by 2-thioxanthine: biochemical and X-ray structural characterization. Nucleic Acids Res. 2014;42(16):10748-61. doi: 10.1093/nar/gku613. Epub 2014 Aug, 20. PMID:25143530 doi:http://dx.doi.org/10.1093/nar/gku613

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4pd2"

Categories: DNA-formamidopyrimidine glycosylase | Castaing, B | Coste, F | Dna glycosylase | Hydrolase-dna complex

@@ Line 1: / Line 1: @@
 ==Crystal structure of a complex between a C248GH LlFpg mutant and a THF containing DNA==
 <StructureSection load='4pd2' size='340' side='right' caption='[[4pd2]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pcz|4pcz]], [[4pdg|4pdg]], [[4pdi|4pdi]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-formamidopyrimidine_glycosylase DNA-formamidopyrimidine glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.23 3.2.2.23] </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=4pd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pd2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pd2 RCSB], [http://www.ebi.ac.uk/pdbsum/4pd2 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=4pd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pd2 OCA], [http://pdbe.org/4pd2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pd2 RCSB], [http://www.ebi.ac.uk/pdbsum/4pd2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pd2 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4pd2" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4pd2

From Proteopedia

Revision as of 17:05, 4 January 2017

Crystal structure of a complex between a C248GH LlFpg mutant and a THF containing DNA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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