6jun: Difference between revisions
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==MsDpo4-DNA complex 3== | |||
<StructureSection load='6jun' size='340' side='right'caption='[[6jun]], [[Resolution|resolution]] 2.51Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6jun]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JUN FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0KX:2-DEOXY-5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]CYTIDINE'>0KX</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6jun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jun OCA], [http://pdbe.org/6jun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jun RCSB], [http://www.ebi.ac.uk/pdbsum/6jun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jun ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/A0QR77_MYCS2 A0QR77_MYCS2]] Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. May be involved in translesional synthesis, in conjunction with the beta clamp from PolIII (By similarity).[HAMAP-Rule:MF_01113] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The presence of ribonucleotides in DNA can lead to genomic instability and cellular lethality. To prevent adventitious rNTP incorporation, the majority of the DNA polymerases (dPols) possess a steric filter. The dPol named MsDpo4 (Mycobacterium smegmatis) naturally lacks this steric filter and hence is capable of rNTP addition. The introduction of the steric filter in MsDpo4 did not result in complete abrogation of the ability of this enzyme to incorporate ribonucleotides. In comparison, DNA polymerase IV (PolIV) from Escherichia coli exhibited stringent selection for deoxyribonucleotides. A comparison of MsDpo4 and PolIV led to the discovery of an additional polar filter responsible for sugar selectivity. Thr43 represents the filter in PolIV and this residue forms interactions with the incoming nucleotide to draw it closer to the enzyme surface. As a result, the 2'-OH in rNTPs will clash with the enzyme surface, and therefore ribonucleotides cannot be accommodated in the active site in a conformation compatible with productive catalysis. The substitution of the equivalent residue in MsDpo4-Cys47, with Thr led to a drastic reduction in the ability of the mycobacterial enzyme to incorporate rNTPs. Overall, our studies evince that the polar filter serves to prevent ribonucleotide incorporation by dPols. | |||
A polar filter in DNA polymerases prevents ribonucleotide incorporation.,Johnson MK, Kottur J, Nair DT Nucleic Acids Res. 2019 Nov 18;47(20):10693-10705. doi: 10.1093/nar/gkz792. PMID:31544946<ref>PMID:31544946</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6jun" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: DNA-directed DNA polymerase]] | |||
[[Category: Large Structures]] | |||
[[Category: Johnson, M K]] | |||
[[Category: Nair, D T]] | |||
[[Category: Dna polymerase]] | |||
[[Category: Replication]] | |||
[[Category: Replication-dna complex]] | |||
Revision as of 09:18, 19 February 2020
MsDpo4-DNA complex 3MsDpo4-DNA complex 3
Structural highlights
Function[A0QR77_MYCS2] Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. May be involved in translesional synthesis, in conjunction with the beta clamp from PolIII (By similarity).[HAMAP-Rule:MF_01113] Publication Abstract from PubMedThe presence of ribonucleotides in DNA can lead to genomic instability and cellular lethality. To prevent adventitious rNTP incorporation, the majority of the DNA polymerases (dPols) possess a steric filter. The dPol named MsDpo4 (Mycobacterium smegmatis) naturally lacks this steric filter and hence is capable of rNTP addition. The introduction of the steric filter in MsDpo4 did not result in complete abrogation of the ability of this enzyme to incorporate ribonucleotides. In comparison, DNA polymerase IV (PolIV) from Escherichia coli exhibited stringent selection for deoxyribonucleotides. A comparison of MsDpo4 and PolIV led to the discovery of an additional polar filter responsible for sugar selectivity. Thr43 represents the filter in PolIV and this residue forms interactions with the incoming nucleotide to draw it closer to the enzyme surface. As a result, the 2'-OH in rNTPs will clash with the enzyme surface, and therefore ribonucleotides cannot be accommodated in the active site in a conformation compatible with productive catalysis. The substitution of the equivalent residue in MsDpo4-Cys47, with Thr led to a drastic reduction in the ability of the mycobacterial enzyme to incorporate rNTPs. Overall, our studies evince that the polar filter serves to prevent ribonucleotide incorporation by dPols. A polar filter in DNA polymerases prevents ribonucleotide incorporation.,Johnson MK, Kottur J, Nair DT Nucleic Acids Res. 2019 Nov 18;47(20):10693-10705. doi: 10.1093/nar/gkz792. PMID:31544946[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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