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New page: left|200px<br /><applet load="1yjm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yjm, resolution 2.20Å" /> '''Crystal structure of...
 
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[[Image:1yjm.gif|left|200px]]<br /><applet load="1yjm" size="450" color="white" frame="true" align="right" spinBox="true"  
[[Image:1yjm.gif|left|200px]]<br /><applet load="1yjm" size="350" color="white" frame="true" align="right" spinBox="true"  
caption="1yjm, resolution 2.20&Aring;" />
caption="1yjm, resolution 2.20&Aring;" />
'''Crystal structure of the FHA domain of mouse polynucleotide kinase in complex with an XRCC4-derived phosphopeptide.'''<br />
'''Crystal structure of the FHA domain of mouse polynucleotide kinase in complex with an XRCC4-derived phosphopeptide.'''<br />


==Overview==
==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==
==About this Structure==
1YJM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with ACE 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=1YJM OCA].  
1YJM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=ACE:'>ACE</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=1YJM OCA].  


==Reference==
==Reference==
Line 14: Line 14:
[[Category: Polynucleotide 5'-hydroxy-kinase]]
[[Category: Polynucleotide 5'-hydroxy-kinase]]
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Bernstein, N.K.]]
[[Category: Bernstein, N K.]]
[[Category: Cass, C.E.]]
[[Category: Cass, C E.]]
[[Category: Cui, D.]]
[[Category: Cui, D.]]
[[Category: Durocher, D.]]
[[Category: Durocher, D.]]
[[Category: Galicia, S.]]
[[Category: Galicia, S.]]
[[Category: Glover, J.N.M.]]
[[Category: Glover, J N.M.]]
[[Category: Green, R.]]
[[Category: Green, R.]]
[[Category: Karimi-Busheri, F.]]
[[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: Weinfeld, M.]]
[[Category: Williams, R.S.]]
[[Category: Williams, R S.]]
[[Category: ACE]]
[[Category: ACE]]
[[Category: fha domain]]
[[Category: fha domain]]
Line 32: Line 32:
[[Category: xrcc4 phosphopeptide]]
[[Category: xrcc4 phosphopeptide]]


''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 06:50:19 2007''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:06:00 2008''