1wei: Difference between revisions

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[[Image:1wei.jpg|left|200px]]<br /><applet load="1wei" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1wei.jpg|left|200px]]<br /><applet load="1wei" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1wei, resolution 1.45Å" />

'''Catalytic Domain Of Muty From Escherichia Coli K20A Mutant Complexed To Adenine'''<br />

==Overview==

The Escherichia coli adenine DNA glycosylase, MutY, plays an important, role in the maintenance of genomic stability by catalyzing the removal of, adenine opposite 8-oxo-7,8-dihydroguanine or guanine in duplex DNA., Although the x-ray crystal structure of the catalytic domain of MutY, revealed a mechanism for catalysis of the glycosyl bond, it appeared that, several opportunistically positioned lysine side chains could participate, in a secondary beta-elimination reaction. In this investigation, it is, established via site-directed mutagenesis and the determination of a, 1.35-A structure of MutY in complex with adenine that the abasic site, (apurinic/apyrimidinic) lyase activity is alternatively regulated by two, lysines, Lys142 and Lys20. Analyses of the crystallographic structure also, suggest a role for Glu161 in the apurinic/apyrimidinic lyase chemistry., The beta-elimination reaction is structurally and chemically uncoupled, from the initial glycosyl bond scission, indicating that this reaction, occurs as a consequence of active site plasticity and slow dissociation of, the product complex. MutY with either the K142A or K20A mutation still, catalyzes beta and beta-delta elimination reactions, and both mutants can, be trapped as covalent enzyme-DNA intermediates by chemical reduction. The, trapping was observed to occur both pre- and post-phosphodiester bond, scission, establishing that both of these intermediates have significant, half-lives. Thus, the final spectrum of DNA products generated reflects, the outcome of a delicate balance of closely related equilibrium, constants.

The Escherichia coli adenine DNA glycosylase, MutY, plays an important role in the maintenance of genomic stability by catalyzing the removal of adenine opposite 8-oxo-7,8-dihydroguanine or guanine in duplex DNA. Although the x-ray crystal structure of the catalytic domain of MutY revealed a mechanism for catalysis of the glycosyl bond, it appeared that several opportunistically positioned lysine side chains could participate in a secondary beta-elimination reaction. In this investigation, it is established via site-directed mutagenesis and the determination of a 1.35-A structure of MutY in complex with adenine that the abasic site (apurinic/apyrimidinic) lyase activity is alternatively regulated by two lysines, Lys142 and Lys20. Analyses of the crystallographic structure also suggest a role for Glu161 in the apurinic/apyrimidinic lyase chemistry. The beta-elimination reaction is structurally and chemically uncoupled from the initial glycosyl bond scission, indicating that this reaction occurs as a consequence of active site plasticity and slow dissociation of the product complex. MutY with either the K142A or K20A mutation still catalyzes beta and beta-delta elimination reactions, and both mutants can be trapped as covalent enzyme-DNA intermediates by chemical reduction. The trapping was observed to occur both pre- and post-phosphodiester bond scission, establishing that both of these intermediates have significant half-lives. Thus, the final spectrum of DNA products generated reflects the outcome of a delicate balance of closely related equilibrium constants.

==About this Structure==

1WEI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with ADE, EDO and SF4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1WEI OCA].

1WEI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=ADE:'>ADE</scene>, <scene name='pdbligand=EDO:'>EDO</scene> and <scene name='pdbligand=SF4:'>SF4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WEI OCA].

==Reference==

Line 13:

[[Category: Escherichia coli]]

[[Category: Single protein]]

[[Category: Arvai, A.S.]]

[[Category: Arvai, A S.]]

[[Category: Hitomi, K.]]

[[Category: Tainer, J.A.]]

[[Category: Tainer, J A.]]

[[Category: ADE]]

[[Category: EDO]]

Line 21:

[[Category: hydrolase]]

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@@ Line 1: / Line 1: @@
-[[Image:1wei.jpg|left|200px]]<br /><applet load="1wei" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1wei.jpg|left|200px]]<br /><applet load="1wei" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1wei, resolution 1.45&Aring;" />
 '''Catalytic Domain Of Muty From Escherichia Coli K20A Mutant Complexed To Adenine'''<br />
 ==Overview==
-The Escherichia coli adenine DNA glycosylase, MutY, plays an important, role in the maintenance of genomic stability by catalyzing the removal of, adenine opposite 8-oxo-7,8-dihydroguanine or guanine in duplex DNA., Although the x-ray crystal structure of the catalytic domain of MutY, revealed a mechanism for catalysis of the glycosyl bond, it appeared that, several opportunistically positioned lysine side chains could participate, in a secondary beta-elimination reaction. In this investigation, it is, established via site-directed mutagenesis and the determination of a, 1.35-A structure of MutY in complex with adenine that the abasic site, (apurinic/apyrimidinic) lyase activity is alternatively regulated by two, lysines, Lys142 and Lys20. Analyses of the crystallographic structure also, suggest a role for Glu161 in the apurinic/apyrimidinic lyase chemistry., The beta-elimination reaction is structurally and chemically uncoupled, from the initial glycosyl bond scission, indicating that this reaction, occurs as a consequence of active site plasticity and slow dissociation of, the product complex. MutY with either the K142A or K20A mutation still, catalyzes beta and beta-delta elimination reactions, and both mutants can, be trapped as covalent enzyme-DNA intermediates by chemical reduction. The, trapping was observed to occur both pre- and post-phosphodiester bond, scission, establishing that both of these intermediates have significant, half-lives. Thus, the final spectrum of DNA products generated reflects, the outcome of a delicate balance of closely related equilibrium, constants.
+The Escherichia coli adenine DNA glycosylase, MutY, plays an important role in the maintenance of genomic stability by catalyzing the removal of adenine opposite 8-oxo-7,8-dihydroguanine or guanine in duplex DNA. Although the x-ray crystal structure of the catalytic domain of MutY revealed a mechanism for catalysis of the glycosyl bond, it appeared that several opportunistically positioned lysine side chains could participate in a secondary beta-elimination reaction. In this investigation, it is established via site-directed mutagenesis and the determination of a 1.35-A structure of MutY in complex with adenine that the abasic site (apurinic/apyrimidinic) lyase activity is alternatively regulated by two lysines, Lys142 and Lys20. Analyses of the crystallographic structure also suggest a role for Glu161 in the apurinic/apyrimidinic lyase chemistry. The beta-elimination reaction is structurally and chemically uncoupled from the initial glycosyl bond scission, indicating that this reaction occurs as a consequence of active site plasticity and slow dissociation of the product complex. MutY with either the K142A or K20A mutation still catalyzes beta and beta-delta elimination reactions, and both mutants can be trapped as covalent enzyme-DNA intermediates by chemical reduction. The trapping was observed to occur both pre- and post-phosphodiester bond scission, establishing that both of these intermediates have significant half-lives. Thus, the final spectrum of DNA products generated reflects the outcome of a delicate balance of closely related equilibrium constants.
 ==About this Structure==
-WEI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with ADE, EDO and SF4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1WEI OCA].
+WEI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=ADE:'>ADE</scene>, <scene name='pdbligand=EDO:'>EDO</scene> and <scene name='pdbligand=SF4:'>SF4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WEI OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Escherichia coli]]
 [[Category: Single protein]]
-[[Category: Arvai, A.S.]]
+[[Category: Arvai, A S.]]
 [[Category: Hitomi, K.]]
-[[Category: Tainer, J.A.]]
+[[Category: Tainer, J A.]]
 [[Category: ADE]]
 [[Category: EDO]]
@@ Line 21: / Line 21: @@
 [[Category: hydrolase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 05:21:08 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:43:24 2008''