1xc8
From Proteopedia
(New page: 200px<br /><applet load="1xc8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xc8, resolution 1.95Å" /> '''CRYSTAL STRUCTURE CO...) |
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| - | [[Image:1xc8.gif|left|200px]]<br /><applet load="1xc8" size=" | + | [[Image:1xc8.gif|left|200px]]<br /><applet load="1xc8" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xc8, resolution 1.95Å" /> | caption="1xc8, resolution 1.95Å" /> | ||
'''CRYSTAL STRUCTURE COMPLEX BETWEEN THE WILD-TYPE LACTOCOCCUS LACTIS FPG (MUTM) AND A FAPY-DG CONTAINING DNA'''<br /> | '''CRYSTAL STRUCTURE COMPLEX BETWEEN THE WILD-TYPE LACTOCOCCUS LACTIS FPG (MUTM) AND A FAPY-DG CONTAINING DNA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that | + | Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that excises oxidized purines such as 7,8-dihydro-8-oxoguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) from damaged DNA. Here, we report the crystal structure of the Fpg protein from Lactococcus lactis (LlFpg) bound to a carbocyclic FapydG (cFapydG)-containing DNA. The structure reveals that Fpg stabilizes the cFapydG nucleoside into an extrahelical conformation inside its substrate binding pocket. In contrast to the recognition of the 8-oxodG lesion, which is bound with the glycosidic bond in a syn conformation, the cFapydG lesion displays in the complex an anti conformation. Furthermore, Fpg establishes interactions with all the functional groups of the FapyG base lesion, which can be classified in two categories: (i) those specifying a purine-derived lesion (here a guanine) involved in the Watson-Crick face recognition of the lesion and probably contributing to an optimal orientation of the pyrimidine ring moiety in the binding pocket and (ii) those specifying the imidazole ring-opened moiety of FapyG and probably participating also in the rotameric selection of the FapydG nucleobase. These interactions involve strictly conserved Fpg residues and structural water molecules mediated interactions. The significant differences between the Fpg recognition modes of 8-oxodG and FapydG provide new insights into the Fpg substrate specificity. |
==About this Structure== | ==About this Structure== | ||
| - | 1XC8 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:// | + | 1XC8 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=1XC8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protein-dna complex; glycosylase; fapy]] | [[Category: protein-dna complex; glycosylase; fapy]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:53:12 2008'' |
Revision as of 13:53, 21 February 2008
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CRYSTAL STRUCTURE COMPLEX BETWEEN THE WILD-TYPE LACTOCOCCUS LACTIS FPG (MUTM) AND A FAPY-DG CONTAINING DNA
Overview
Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that excises oxidized purines such as 7,8-dihydro-8-oxoguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) from damaged DNA. Here, we report the crystal structure of the Fpg protein from Lactococcus lactis (LlFpg) bound to a carbocyclic FapydG (cFapydG)-containing DNA. The structure reveals that Fpg stabilizes the cFapydG nucleoside into an extrahelical conformation inside its substrate binding pocket. In contrast to the recognition of the 8-oxodG lesion, which is bound with the glycosidic bond in a syn conformation, the cFapydG lesion displays in the complex an anti conformation. Furthermore, Fpg establishes interactions with all the functional groups of the FapyG base lesion, which can be classified in two categories: (i) those specifying a purine-derived lesion (here a guanine) involved in the Watson-Crick face recognition of the lesion and probably contributing to an optimal orientation of the pyrimidine ring moiety in the binding pocket and (ii) those specifying the imidazole ring-opened moiety of FapyG and probably participating also in the rotameric selection of the FapydG nucleobase. These interactions involve strictly conserved Fpg residues and structural water molecules mediated interactions. The significant differences between the Fpg recognition modes of 8-oxodG and FapydG provide new insights into the Fpg substrate specificity.
About this Structure
1XC8 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 basis for the recognition of the FapydG lesion (2,6-diamino-4-hydroxy-5-formamidopyrimidine) by formamidopyrimidine-DNA glycosylase., Coste F, Ober M, Carell T, Boiteux S, Zelwer C, Castaing B, J Biol Chem. 2004 Oct 15;279(42):44074-83. Epub 2004 Jul 10. PMID:15249553
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