1pm5
From Proteopedia
(New page: 200px<br /><applet load="1pm5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pm5, resolution 1.95Å" /> '''Crystal structure of...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1pm5.gif|left|200px]]<br /><applet load="1pm5" size=" | + | [[Image:1pm5.gif|left|200px]]<br /><applet load="1pm5" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1pm5, resolution 1.95Å" /> | caption="1pm5, resolution 1.95Å" /> | ||
'''Crystal structure of wild type Lactococcus lactis Fpg complexed to a tetrahydrofuran containing DNA'''<br /> | '''Crystal structure of wild type Lactococcus lactis Fpg complexed to a tetrahydrofuran containing DNA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Fpg is a DNA glycosylase that recognizes and excises the mutagenic | + | Fpg is a DNA glycosylase that recognizes and excises the mutagenic 8-oxoguanine (8-oxoG) and the potentially lethal formamidopyrimidic residues (Fapy). Fpg is also associated with an AP lyase activity which successively cleaves the abasic (AP) site at the 3' and 5' sides by betadelta-elimination. Here, we present the high-resolution crystal structures of the wild-type and the P1G defective mutant of Fpg from Lactococcus lactis bound to 14mer DNA duplexes containing either a tetrahydrofuran (THF) or 1,3-propanediol (Pr) AP site analogues. Structures show that THF is less extrahelical than Pr and its backbone C5'-C4'-C3' diverges significantly from those of Pr, rAP, 8-oxodG and FapydG. Clearly, the heterocyclic oxygen of THF is pushed back by the carboxylate of the strictly conserved E2 residue. We can propose that the ring-opened form of the damaged deoxyribose is the structure active form of the sugar for Fpg catalysis process. Both structural and functional data suggest that the first step of catalysis mediated by Fpg involves the expulsion of the O4' leaving group facilitated by general acid catalysis (involving E2), rather than the immediate cleavage of the N-glycosic bond of the damaged nucleoside. |
==About this Structure== | ==About this Structure== | ||
| - | 1PM5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lactococcus_lactis Lactococcus lactis] with ZN and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1PM5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lactococcus_lactis Lactococcus lactis] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PM5 OCA]. |
==Reference== | ==Reference== | ||
| Line 15: | Line 15: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Castaing, B.]] | [[Category: Castaing, B.]] | ||
| - | [[Category: Jesus-Tran, K | + | [[Category: Jesus-Tran, K Pereira de.]] |
[[Category: Serre, L.]] | [[Category: Serre, L.]] | ||
[[Category: Zelwer, C.]] | [[Category: Zelwer, C.]] | ||
| Line 25: | Line 25: | ||
[[Category: mutm]] | [[Category: mutm]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:30:10 2008'' |
Revision as of 12:30, 21 February 2008
|
Crystal structure of wild type Lactococcus lactis Fpg complexed to a tetrahydrofuran containing DNA
Overview
Fpg is a DNA glycosylase that recognizes and excises the mutagenic 8-oxoguanine (8-oxoG) and the potentially lethal formamidopyrimidic residues (Fapy). Fpg is also associated with an AP lyase activity which successively cleaves the abasic (AP) site at the 3' and 5' sides by betadelta-elimination. Here, we present the high-resolution crystal structures of the wild-type and the P1G defective mutant of Fpg from Lactococcus lactis bound to 14mer DNA duplexes containing either a tetrahydrofuran (THF) or 1,3-propanediol (Pr) AP site analogues. Structures show that THF is less extrahelical than Pr and its backbone C5'-C4'-C3' diverges significantly from those of Pr, rAP, 8-oxodG and FapydG. Clearly, the heterocyclic oxygen of THF is pushed back by the carboxylate of the strictly conserved E2 residue. We can propose that the ring-opened form of the damaged deoxyribose is the structure active form of the sugar for Fpg catalysis process. Both structural and functional data suggest that the first step of catalysis mediated by Fpg involves the expulsion of the O4' leaving group facilitated by general acid catalysis (involving E2), rather than the immediate cleavage of the N-glycosic bond of the damaged nucleoside.
About this Structure
1PM5 is a Single protein structure of sequence from Lactococcus lactis with and as ligands. Active as DNA-formamidopyrimidine glycosylase, with EC number 3.2.2.23 Full crystallographic information is available from OCA.
Reference
Structural insights into abasic site for Fpg specific binding and catalysis: comparative high-resolution crystallographic studies of Fpg bound to various models of abasic site analogues-containing DNA., Pereira de Jesus K, Serre L, Zelwer C, Castaing B, Nucleic Acids Res. 2005 Oct 20;33(18):5936-44. Print 2005. PMID:16243784
Page seeded by OCA on Thu Feb 21 14:30:10 2008
