1pu6
From Proteopedia
(New page: 200px<br /><applet load="1pu6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pu6, resolution 1.64Å" /> '''Crystal structure of...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1pu6.gif|left|200px]]<br /><applet load="1pu6" size=" | + | [[Image:1pu6.gif|left|200px]]<br /><applet load="1pu6" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1pu6, resolution 1.64Å" /> | caption="1pu6, resolution 1.64Å" /> | ||
'''Crystal structure of H.pylori 3-methyladenine DNA glycosylase (MagIII)'''<br /> | '''Crystal structure of H.pylori 3-methyladenine DNA glycosylase (MagIII)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | DNA glycosylases catalyze the excision of chemically modified bases from | + | DNA glycosylases catalyze the excision of chemically modified bases from DNA. Although most glycosylases are specific to a particular base, the 3-methyladenine (m3A) DNA glycosylases include both highly specific enzymes acting on a single modified base, and enzymes with broader specificity for alkylation-damaged DNA. Our structural understanding of these different enzymatic specificities is currently limited to crystal and NMR structures of the unliganded enzymes and complexes with abasic DNA inhibitors. Presented here are high-resolution crystal structures of the m3A DNA glycosylase from Helicobacter pylori (MagIII) in the unliganded form and bound to alkylated bases 3,9-dimethyladenine and 1,N6-ethenoadenine. These are the first structures of a nucleobase bound in the active site of a m3A glycosylase belonging to the helix-hairpin-helix superfamily. MagIII achieves its specificity for positively-charged m3A not by direct interactions with purine or methyl substituent atoms, but rather by stacking the base between two aromatic side chains in a pocket that excludes 7-methylguanine. We report base excision and DNA binding activities of MagIII active site mutants, together with a structural comparison of the HhH glycosylases. |
==About this Structure== | ==About this Structure== | ||
| - | 1PU6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Helicobacter_pylori Helicobacter pylori] with CL, BME and MPD as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1PU6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Helicobacter_pylori Helicobacter pylori] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=BME:'>BME</scene> and <scene name='pdbligand=MPD:'>MPD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PU6 OCA]. |
==Reference== | ==Reference== | ||
| Line 13: | Line 13: | ||
[[Category: Helicobacter pylori]] | [[Category: Helicobacter pylori]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Eichman, B | + | [[Category: Eichman, B F.]] |
[[Category: Ellenberger, T.]] | [[Category: Ellenberger, T.]] | ||
| - | [[Category: Radicella, J | + | [[Category: Radicella, J P.]] |
| - | [[Category: Rourke, E | + | [[Category: Rourke, E J.O.]] |
[[Category: BME]] | [[Category: BME]] | ||
[[Category: CL]] | [[Category: CL]] | ||
| Line 25: | Line 25: | ||
[[Category: helix-hairpin-helix]] | [[Category: helix-hairpin-helix]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:32:35 2008'' |
Revision as of 12:32, 21 February 2008
|
Crystal structure of H.pylori 3-methyladenine DNA glycosylase (MagIII)
Overview
DNA glycosylases catalyze the excision of chemically modified bases from DNA. Although most glycosylases are specific to a particular base, the 3-methyladenine (m3A) DNA glycosylases include both highly specific enzymes acting on a single modified base, and enzymes with broader specificity for alkylation-damaged DNA. Our structural understanding of these different enzymatic specificities is currently limited to crystal and NMR structures of the unliganded enzymes and complexes with abasic DNA inhibitors. Presented here are high-resolution crystal structures of the m3A DNA glycosylase from Helicobacter pylori (MagIII) in the unliganded form and bound to alkylated bases 3,9-dimethyladenine and 1,N6-ethenoadenine. These are the first structures of a nucleobase bound in the active site of a m3A glycosylase belonging to the helix-hairpin-helix superfamily. MagIII achieves its specificity for positively-charged m3A not by direct interactions with purine or methyl substituent atoms, but rather by stacking the base between two aromatic side chains in a pocket that excludes 7-methylguanine. We report base excision and DNA binding activities of MagIII active site mutants, together with a structural comparison of the HhH glycosylases.
About this Structure
1PU6 is a Single protein structure of sequence from Helicobacter pylori with , and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structures of 3-methyladenine DNA glycosylase MagIII and the recognition of alkylated bases., Eichman BF, O'Rourke EJ, Radicella JP, Ellenberger T, EMBO J. 2003 Oct 1;22(19):4898-909. PMID:14517230
Page seeded by OCA on Thu Feb 21 14:32:35 2008
