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Crystal Structure Of Uracil-DNA Glycosylase From Thermus Thermophilus HB8

OverviewOverview

Uracil-DNA glycosylase (UDG; EC 3.2.2.-) removes uracil from DNA to initiate DNA base excision repair. Since hydrolytic deamination of cytosine to uracil is one of the most frequent DNA-damaging events in all cells, UDG is an essential enzyme for maintaining the integrity of genomic information. For the first time, we report the crystal structure of a family 4 UDG from Thermus thermophilus HB8 (TthUDG) complexed with uracil, solved at 1.5 angstroms resolution. As opposed to UDG enzymes in its other families, TthUDG possesses a [4Fe-4S] cluster. This iron-sulfur cluster, which is distant from the active site, interacts with loop structures and has been suggested to be unessential to the activity but necessary for stabilizing the loop structures. In addition to the iron-sulfur cluster, salt-bridges and ion pairs on the molecular surface and the presence of proline on loops and turns is thought to contribute to the enzyme's thermostability. Despite very low levels of sequence identity with Escherichia coli and human UDGs (family 1) and E.coli G:T/U mismatch-specific DNA glycosylase (MUG) (family 2), the topology and order of secondary structures of TthUDG are similar to those of these distant relatives. Furthermore, the coordinates of the core structure formed by beta-strands are almost the same. Positive charge is distributed over the active-site groove, where TthUDG would bind DNA strands, as do UDG enzymes in other families. TthUDG recognizes uracil specifically in the same manner as does human UDG (family 1), rather than guanine in the complementary strand DNA, as does E.coli MUG (family 2). These results suggest that the mechanism by which family 4 UDGs remove uracils from DNA is similar to that of family 1 enzymes.

About this StructureAbout this Structure

1UI1 is a Single protein structure of sequence from Thermus thermophilus with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of a family 4 uracil-DNA glycosylase from Thermus thermophilus HB8., Hoseki J, Okamoto A, Masui R, Shibata T, Inoue Y, Yokoyama S, Kuramitsu S, J Mol Biol. 2003 Oct 24;333(3):515-26. PMID:14556741

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 '''Crystal Structure Of Uracil-DNA Glycosylase From Thermus Thermophilus HB8'''<br />
 ==Overview==
-Uracil-DNA glycosylase (UDG; EC 3.2.2.-) removes uracil from DNA to, initiate DNA base excision repair. Since hydrolytic deamination of, cytosine to uracil is one of the most frequent DNA-damaging events in all, cells, UDG is an essential enzyme for maintaining the integrity of genomic, information. For the first time, we report the crystal structure of a, family 4 UDG from Thermus thermophilus HB8 (TthUDG) complexed with uracil, solved at 1.5 angstroms resolution. As opposed to UDG enzymes in its other, families, TthUDG possesses a [4Fe-4S] cluster. This iron-sulfur cluster, which is distant from the active site, interacts with loop structures and, has been suggested to be unessential to the activity but necessary for, stabilizing the loop structures. In addition to the iron-sulfur cluster, salt-bridges and ion pairs on the molecular surface and the presence of, proline on loops and turns is thought to contribute to the enzyme's, thermostability. Despite very low levels of sequence identity with, Escherichia coli and human UDGs (family 1) and E.coli G:T/U, mismatch-specific DNA glycosylase (MUG) (family 2), the topology and order, of secondary structures of TthUDG are similar to those of these distant, relatives. Furthermore, the coordinates of the core structure formed by, beta-strands are almost the same. Positive charge is distributed over the, active-site groove, where TthUDG would bind DNA strands, as do UDG enzymes, in other families. TthUDG recognizes uracil specifically in the same, manner as does human UDG (family 1), rather than guanine in the, complementary strand DNA, as does E.coli MUG (family 2). These results, suggest that the mechanism by which family 4 UDGs remove uracils from DNA, is similar to that of family 1 enzymes.
+Uracil-DNA glycosylase (UDG; EC 3.2.2.-) removes uracil from DNA to initiate DNA base excision repair. Since hydrolytic deamination of cytosine to uracil is one of the most frequent DNA-damaging events in all cells, UDG is an essential enzyme for maintaining the integrity of genomic information. For the first time, we report the crystal structure of a family 4 UDG from Thermus thermophilus HB8 (TthUDG) complexed with uracil, solved at 1.5 angstroms resolution. As opposed to UDG enzymes in its other families, TthUDG possesses a [4Fe-4S] cluster. This iron-sulfur cluster, which is distant from the active site, interacts with loop structures and has been suggested to be unessential to the activity but necessary for stabilizing the loop structures. In addition to the iron-sulfur cluster, salt-bridges and ion pairs on the molecular surface and the presence of proline on loops and turns is thought to contribute to the enzyme's thermostability. Despite very low levels of sequence identity with Escherichia coli and human UDGs (family 1) and E.coli G:T/U mismatch-specific DNA glycosylase (MUG) (family 2), the topology and order of secondary structures of TthUDG are similar to those of these distant relatives. Furthermore, the coordinates of the core structure formed by beta-strands are almost the same. Positive charge is distributed over the active-site groove, where TthUDG would bind DNA strands, as do UDG enzymes in other families. TthUDG recognizes uracil specifically in the same manner as does human UDG (family 1), rather than guanine in the complementary strand DNA, as does E.coli MUG (family 2). These results suggest that the mechanism by which family 4 UDGs remove uracils from DNA is similar to that of family 1 enzymes.
 ==About this Structure==
-UI1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with SF4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UI1 OCA].
+UI1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with <scene name='pdbligand=SF4:'>SF4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UI1 OCA].
 ==Reference==
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 [[Category: Masui, R.]]
 [[Category: Okamoto, A.]]
-[[Category: RSGI, RIKEN.Structural.Genomics/Proteomics.Initiative.]]
+[[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]]
 [[Category: Shibata, T.]]
 [[Category: Yokoyama, S.]]
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 [[Category: uracil-dna glycosylase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 04:02:04 2007''
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