1nk4: Difference between revisions

Revision as of 15:06, 21 February 2008

GUANINE-GUANINE MISMATCH AT THE POLYMERASE ACTIVE SITE

OverviewOverview

Accurate DNA replication is essential for genomic stability. One mechanism by which high-fidelity DNA polymerases maintain replication accuracy involves stalling of the polymerase in response to covalent incorporation of mismatched base pairs, thereby favoring subsequent mismatch excision. Some polymerases retain a "short-term memory" of replication errors, responding to mismatches up to four base pairs in from the primer terminus. Here we a present a structural characterization of all 12 possible mismatches captured at the growing primer terminus in the active site of a polymerase. Our observations suggest four mechanisms that lead to mismatch-induced stalling of the polymerase. Furthermore, we have observed the effects of extending a mismatch up to six base pairs from the primer terminus and find that long-range distortions in the DNA transmit the presence of the mismatch back to the enzyme active site, suggesting the structural basis for the short-term memory of replication errors.

About this StructureAbout this Structure

1NK4 is a Protein complex structure of sequences from Geobacillus stearothermophilus with , and as ligands. Active as DNA-directed DNA polymerase, with EC number 2.7.7.7 Full crystallographic information is available from OCA.

ReferenceReference

Structures of mismatch replication errors observed in a DNA polymerase., Johnson SJ, Beese LS, Cell. 2004 Mar 19;116(6):803-16. PMID:15035983

Page seeded by OCA on Thu Feb 21 14:06:56 2008

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OCA

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-[[Image:1nk4.gif|left|200px]]<br /><applet load="1nk4" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1nk4.gif|left|200px]]<br /><applet load="1nk4" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1nk4, resolution 1.60&Aring;" />
 '''GUANINE-GUANINE MISMATCH AT THE POLYMERASE ACTIVE SITE'''<br />
 ==Overview==
-Accurate DNA replication is essential for genomic stability. One mechanism, by which high-fidelity DNA polymerases maintain replication accuracy, involves stalling of the polymerase in response to covalent incorporation, of mismatched base pairs, thereby favoring subsequent mismatch excision., Some polymerases retain a "short-term memory" of replication errors, responding to mismatches up to four base pairs in from the primer, terminus. Here we a present a structural characterization of all 12, possible mismatches captured at the growing primer terminus in the active, site of a polymerase. Our observations suggest four mechanisms that lead, to mismatch-induced stalling of the polymerase. Furthermore, we have, observed the effects of extending a mismatch up to six base pairs from the, primer terminus and find that long-range distortions in the DNA transmit, the presence of the mismatch back to the enzyme active site, suggesting, the structural basis for the short-term memory of replication errors.
+Accurate DNA replication is essential for genomic stability. One mechanism by which high-fidelity DNA polymerases maintain replication accuracy involves stalling of the polymerase in response to covalent incorporation of mismatched base pairs, thereby favoring subsequent mismatch excision. Some polymerases retain a "short-term memory" of replication errors, responding to mismatches up to four base pairs in from the primer terminus. Here we a present a structural characterization of all 12 possible mismatches captured at the growing primer terminus in the active site of a polymerase. Our observations suggest four mechanisms that lead to mismatch-induced stalling of the polymerase. Furthermore, we have observed the effects of extending a mismatch up to six base pairs from the primer terminus and find that long-range distortions in the DNA transmit the presence of the mismatch back to the enzyme active site, suggesting the structural basis for the short-term memory of replication errors.
 ==About this Structure==
-NK4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with SUC, SO4 and MG as [http://en.wikipedia.org/wiki/ligands ligands]. 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NK4 OCA].
+NK4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with <scene name='pdbligand=SUC:'>SUC</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1NK4 OCA].
 ==Reference==
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 [[Category: Geobacillus stearothermophilus]]
 [[Category: Protein complex]]
-[[Category: Beese, L.S.]]
+[[Category: Beese, L S.]]
-[[Category: Johnson, S.J.]]
+[[Category: Johnson, S J.]]
 [[Category: MG]]
 [[Category: SO4]]
@@ Line 25: / Line 25: @@
 [[Category: protein-dna complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 23:16:49 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:06:56 2008''