1yj5: Difference between revisions

Line 1:

[[Image:1yj5.gif|left|200px]]<br /><applet load="1yj5" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1yj5.gif|left|200px]]<br /><applet load="1yj5" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1yj5, resolution 2.80Å" />

'''Molecular architecture of mammalian polynucleotide kinase, a DNA repair enzyme'''<br />

==Overview==

Mammalian polynucleotide kinase (PNK) is a key component of both the base, excision repair (BER) and nonhomologous end-joining (NHEJ) DNA repair, pathways. PNK acts as a 5'-kinase/3'-phosphatase to create, 5'-phosphate/3'-hydroxyl termini, which are a necessary prerequisite for, ligation during repair. PNK is recruited to repair complexes through, interactions between its N-terminal FHA domain and phosphorylated, components of either pathway. Here, we describe the crystal structure of, intact mammalian PNK and a structure of the PNK FHA bound to a cognate, phosphopeptide. The kinase domain has a broad substrate binding pocket, which preferentially recognizes double-stranded substrates with recessed, 5' termini. In contrast, the phosphatase domain efficiently, dephosphorylates single-stranded 3'-phospho termini as well as, double-stranded substrates. The FHA domain is linked to the, kinase/phosphatase catalytic domain by a flexible tether, and it exhibits, a mode of target selection based on electrostatic complementarity between, the binding surface and the phosphothreonine peptide.

Mammalian polynucleotide kinase (PNK) is a key component of both the base excision repair (BER) and nonhomologous end-joining (NHEJ) DNA repair pathways. PNK acts as a 5'-kinase/3'-phosphatase to create 5'-phosphate/3'-hydroxyl termini, which are a necessary prerequisite for ligation during repair. PNK is recruited to repair complexes through interactions between its N-terminal FHA domain and phosphorylated components of either pathway. Here, we describe the crystal structure of intact mammalian PNK and a structure of the PNK FHA bound to a cognate phosphopeptide. The kinase domain has a broad substrate binding pocket, which preferentially recognizes double-stranded substrates with recessed 5' termini. In contrast, the phosphatase domain efficiently dephosphorylates single-stranded 3'-phospho termini as well as double-stranded substrates. The FHA domain is linked to the kinase/phosphatase catalytic domain by a flexible tether, and it exhibits a mode of target selection based on electrostatic complementarity between the binding surface and the phosphothreonine peptide.

==About this Structure==

1YJ5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Polynucleotide_5'-hydroxy-kinase Polynucleotide 5'-hydroxy-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.78 2.7.1.78] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1YJ5 OCA].

1YJ5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Polynucleotide_5'-hydroxy-kinase Polynucleotide 5'-hydroxy-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.78 2.7.1.78] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YJ5 OCA].

==Reference==

Line 14:

[[Category: Polynucleotide 5'-hydroxy-kinase]]

[[Category: Protein complex]]

[[Category: Bernstein, N.K.]]

[[Category: Bernstein, N K.]]

[[Category: Cass, C.E.]]

[[Category: Cass, C E.]]

[[Category: Cui, D.]]

[[Category: Durocher, D.]]

[[Category: Galicia, S.]]

[[Category: Glover, J.N.M.]]

[[Category: Glover, J N.M.]]

[[Category: Green, R.]]

[[Category: Karimi-Busheri, F.]]

[[Category: Koch, C.A.]]

[[Category: Koch, C A.]]

[[Category: Mani, R.S.]]

[[Category: Mani, R S.]]

[[Category: Rakovszky, M.L.]]

[[Category: Rakovszky, M L.]]

[[Category: Weinfeld, M.]]

[[Category: Williams, R.S.]]

[[Category: Williams, R S.]]

[[Category: SO4]]

[[Category: beta sandwich]]

[[Category: p-loop]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 06:49:~~34 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:05:52 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1yj5.gif|left|200px]]<br /><applet load="1yj5" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1yj5.gif|left|200px]]<br /><applet load="1yj5" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1yj5, resolution 2.80&Aring;" />
 '''Molecular architecture of mammalian polynucleotide kinase, a DNA repair enzyme'''<br />
 ==Overview==
-Mammalian polynucleotide kinase (PNK) is a key component of both the base, excision repair (BER) and nonhomologous end-joining (NHEJ) DNA repair, pathways. PNK acts as a 5'-kinase/3'-phosphatase to create, 5'-phosphate/3'-hydroxyl termini, which are a necessary prerequisite for, ligation during repair. PNK is recruited to repair complexes through, interactions between its N-terminal FHA domain and phosphorylated, components of either pathway. Here, we describe the crystal structure of, intact mammalian PNK and a structure of the PNK FHA bound to a cognate, phosphopeptide. The kinase domain has a broad substrate binding pocket, which preferentially recognizes double-stranded substrates with recessed, 5' termini. In contrast, the phosphatase domain efficiently, dephosphorylates single-stranded 3'-phospho termini as well as, double-stranded substrates. The FHA domain is linked to the, kinase/phosphatase catalytic domain by a flexible tether, and it exhibits, a mode of target selection based on electrostatic complementarity between, the binding surface and the phosphothreonine peptide.
+Mammalian polynucleotide kinase (PNK) is a key component of both the base excision repair (BER) and nonhomologous end-joining (NHEJ) DNA repair pathways. PNK acts as a 5'-kinase/3'-phosphatase to create 5'-phosphate/3'-hydroxyl termini, which are a necessary prerequisite for ligation during repair. PNK is recruited to repair complexes through interactions between its N-terminal FHA domain and phosphorylated components of either pathway. Here, we describe the crystal structure of intact mammalian PNK and a structure of the PNK FHA bound to a cognate phosphopeptide. The kinase domain has a broad substrate binding pocket, which preferentially recognizes double-stranded substrates with recessed 5' termini. In contrast, the phosphatase domain efficiently dephosphorylates single-stranded 3'-phospho termini as well as double-stranded substrates. The FHA domain is linked to the kinase/phosphatase catalytic domain by a flexible tether, and it exhibits a mode of target selection based on electrostatic complementarity between the binding surface and the phosphothreonine peptide.
 ==About this Structure==
-YJ5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Polynucleotide_5'-hydroxy-kinase Polynucleotide 5'-hydroxy-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.78 2.7.1.78] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1YJ5 OCA].
+YJ5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Polynucleotide_5'-hydroxy-kinase Polynucleotide 5'-hydroxy-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.78 2.7.1.78] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YJ5 OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Polynucleotide 5'-hydroxy-kinase]]
 [[Category: Protein complex]]
-[[Category: Bernstein, N.K.]]
+[[Category: Bernstein, N K.]]
-[[Category: Cass, C.E.]]
+[[Category: Cass, C E.]]
 [[Category: Cui, D.]]
 [[Category: Durocher, D.]]
 [[Category: Galicia, S.]]
-[[Category: Glover, J.N.M.]]
+[[Category: Glover, J N.M.]]
 [[Category: Green, R.]]
 [[Category: Karimi-Busheri, F.]]
-[[Category: Koch, C.A.]]
+[[Category: Koch, C A.]]
-[[Category: Mani, R.S.]]
+[[Category: Mani, R S.]]
-[[Category: Rakovszky, M.L.]]
+[[Category: Rakovszky, M L.]]
 [[Category: Weinfeld, M.]]
-[[Category: Williams, R.S.]]
+[[Category: Williams, R S.]]
 [[Category: SO4]]
 [[Category: beta sandwich]]
 [[Category: p-loop]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 06:49:34 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:05:52 2008''