2g4c
From Proteopedia
(New page: 200px<br /> <applet load="2g4c" size="450" color="white" frame="true" align="right" spinBox="true" caption="2g4c, resolution 3.15Å" /> '''Crystal Structure o...) |
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caption="2g4c, resolution 3.15Å" /> | caption="2g4c, resolution 3.15Å" /> | ||
'''Crystal Structure of human DNA polymerase gamma accessory subunit'''<br /> | '''Crystal Structure of human DNA polymerase gamma accessory subunit'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Mitochondrial DNA polymerase (pol gamma) is the sole DNA polymerase | + | Mitochondrial DNA polymerase (pol gamma) is the sole DNA polymerase responsible for replication and repair of animal mitochondrial DNA. Here, we address the molecular mechanism by which the human holoenzyme achieves high processivity in nucleotide polymerization. We have determined the crystal structure of human pol gamma-beta, the accessory subunit that binds with high affinity to the catalytic core, pol gamma-alpha, to stimulate its activity and enhance holoenzyme processivity. We find that human pol gamma-beta shares a high level of structural similarity to class IIa aminoacyl tRNA synthetases, and forms a dimer in the crystal. A human pol gamma/DNA complex model was developed using the structures of the pol gamma-beta dimer and the bacteriophage T7 DNA polymerase ternary complex, which suggests multiple regions of subunit interaction between pol gamma-beta and the human catalytic core that allow it to encircle the newly synthesized double-stranded DNA, and thereby enhance DNA binding affinity and holoenzyme processivity. Biochemical properties of a novel set of human pol gamma-beta mutants are explained by and test the model, and elucidate the role of the accessory subunit as a novel type of processivity factor in stimulating pol gamma activity and in enhancing processivity. |
==About this Structure== | ==About this Structure== | ||
| - | 2G4C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] Full crystallographic information is available from [http:// | + | 2G4C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G4C OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Fan, L.]] | [[Category: Fan, L.]] | ||
| - | [[Category: Farr, C | + | [[Category: Farr, C L.]] |
| - | [[Category: Kaguni, L | + | [[Category: Kaguni, L S.]] |
| - | [[Category: Tainer, J | + | [[Category: Tainer, J A.]] |
[[Category: aars class ii-like]] | [[Category: aars class ii-like]] | ||
[[Category: alpha and beta protein]] | [[Category: alpha and beta protein]] | ||
[[Category: anti-codon binding domain-like]] | [[Category: anti-codon binding domain-like]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:28:00 2008'' |
Revision as of 15:28, 21 February 2008
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Crystal Structure of human DNA polymerase gamma accessory subunit
Overview
Mitochondrial DNA polymerase (pol gamma) is the sole DNA polymerase responsible for replication and repair of animal mitochondrial DNA. Here, we address the molecular mechanism by which the human holoenzyme achieves high processivity in nucleotide polymerization. We have determined the crystal structure of human pol gamma-beta, the accessory subunit that binds with high affinity to the catalytic core, pol gamma-alpha, to stimulate its activity and enhance holoenzyme processivity. We find that human pol gamma-beta shares a high level of structural similarity to class IIa aminoacyl tRNA synthetases, and forms a dimer in the crystal. A human pol gamma/DNA complex model was developed using the structures of the pol gamma-beta dimer and the bacteriophage T7 DNA polymerase ternary complex, which suggests multiple regions of subunit interaction between pol gamma-beta and the human catalytic core that allow it to encircle the newly synthesized double-stranded DNA, and thereby enhance DNA binding affinity and holoenzyme processivity. Biochemical properties of a novel set of human pol gamma-beta mutants are explained by and test the model, and elucidate the role of the accessory subunit as a novel type of processivity factor in stimulating pol gamma activity and in enhancing processivity.
About this Structure
2G4C is a Single protein structure of sequence from Homo sapiens. Active as DNA-directed DNA polymerase, with EC number 2.7.7.7 Full crystallographic information is available from OCA.
Reference
A novel processive mechanism for DNA synthesis revealed by structure, modeling and mutagenesis of the accessory subunit of human mitochondrial DNA polymerase., Fan L, Kim S, Farr CL, Schaefer KT, Randolph KM, Tainer JA, Kaguni LS, J Mol Biol. 2006 May 19;358(5):1229-43. Epub 2006 Mar 15. PMID:16574152
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