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4q45

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Revision as of 08:54, 24 April 2019

DNA Polymerase- damaged DNA complex

Structural highlights

4q45 is a 6 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	4q43, 4q44
Gene:	dinB (ECOLI)
Activity:	DNA-directed DNA polymerase, with EC number 2.7.7.7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DPO4_ECOLI] 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. Overexpression of polIV results in increased frameshift mutagenesis. It is required for stationary-phase adaptive mutation, which provides the bacterium with flexibility in dealing with environmental stress, enhancing long-term survival and evolutionary fitness. May be involved in translesional synthesis, in conjunction with the beta clamp from PolIII.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The reduction in the efficacy of therapeutic antibiotics represents a global problem of increasing intensity and concern. Nitrofuran antibiotics act primarily through the formation of covalent adducts at the N(2) atom of the deoxyguanosine nucleotide in genomic DNA. These adducts inhibit replicative DNA polymerases (dPols), leading to the death of the prokaryote. N(2)-furfuryl-deoxyguanosine (fdG) represents a stable structural analog of the nitrofuran-induced adducts. Unlike other known dPols, DNA polymerase IV (PolIV) from E. coli can bypass the fdG adduct accurately with high catalytic efficiency. This property of PolIV is central to its role in reducing the sensitivity of E. coli toward nitrofuran antibiotics such as nitrofurazone (NFZ). We present the mechanism used by PolIV to bypass NFZ-induced adducts and thus improve viability of E. coli in the presence of NFZ. Our results can be used to develop specific inhibitors of PolIV that may potentiate the activity of nitrofuran antibiotics.

Unique structural features in DNA polymerase IV enable efficient bypass of the N2 adduct induced by the nitrofurazone antibiotic.,Kottur J, Sharma A, Gore KR, Narayanan N, Samanta B, Pradeepkumar PI, Nair DT Structure. 2015 Jan 6;23(1):56-67. doi: 10.1016/j.str.2014.10.019. Epub 2014 Dec , 11. PMID:25497730^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kim SR, Maenhaut-Michel G, Yamada M, Yamamoto Y, Matsui K, Sofuni T, Nohmi T, Ohmori H. Multiple pathways for SOS-induced mutagenesis in Escherichia coli: an overexpression of dinB/dinP results in strongly enhancing mutagenesis in the absence of any exogenous treatment to damage DNA. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13792-7. PMID:9391106
↑ Napolitano R, Janel-Bintz R, Wagner J, Fuchs RP. All three SOS-inducible DNA polymerases (Pol II, Pol IV and Pol V) are involved in induced mutagenesis. EMBO J. 2000 Nov 15;19(22):6259-65. PMID:11080171 doi:10.1093/emboj/19.22.6259
↑ McKenzie GJ, Lee PL, Lombardo MJ, Hastings PJ, Rosenberg SM. SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification. Mol Cell. 2001 Mar;7(3):571-9. PMID:11463382
↑ Lenne-Samuel N, Wagner J, Etienne H, Fuchs RP. The processivity factor beta controls DNA polymerase IV traffic during spontaneous mutagenesis and translesion synthesis in vivo. EMBO Rep. 2002 Jan;3(1):45-9. Epub 2001 Dec 19. PMID:11751576 doi:10.1093/embo-reports/kvf007
↑ Yeiser B, Pepper ED, Goodman MF, Finkel SE. SOS-induced DNA polymerases enhance long-term survival and evolutionary fitness. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8737-41. Epub 2002 Jun 11. PMID:12060704 doi:10.1073/pnas.092269199
↑ Kottur J, Sharma A, Gore KR, Narayanan N, Samanta B, Pradeepkumar PI, Nair DT. Unique structural features in DNA polymerase IV enable efficient bypass of the N2 adduct induced by the nitrofurazone antibiotic. Structure. 2015 Jan 6;23(1):56-67. doi: 10.1016/j.str.2014.10.019. Epub 2014 Dec , 11. PMID:25497730 doi:http://dx.doi.org/10.1016/j.str.2014.10.019

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4q45"

@@ Line 1: / Line 1: @@
 ==DNA Polymerase- damaged DNA complex==
-<StructureSection load='4q45' size='340' side='right' caption='[[4q45]], [[Resolution|resolution]] 2.18&Aring;' scene=''>
+<StructureSection load='4q45' size='340' side='right'caption='[[4q45]], [[Resolution|resolution]] 2.18&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4q45]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q45 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Q45 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4q45]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q45 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Q45 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1FZ:5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]THYMIDINE'>1FZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=RDG:2-DEOXY-N-(FURAN-2-YLMETHYL)GUANOSINE+5-(DIHYDROGEN+PHOSPHATE)'>RDG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4q43|4q43]], [[4q44|4q44]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dinB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=4q45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q45 OCA], [http://pdbe.org/4q45 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4q45 RCSB], [http://www.ebi.ac.uk/pdbsum/4q45 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4q45 ProSAT]</span></td></tr>
@@ Line 21: / Line 22: @@
 </div>
 <div class="pdbe-citations 4q45" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[DNA polymerase|DNA polymerase]]
 == References ==
 <references/>
@@ Line 26: / Line 30: @@
 </StructureSection>
 [[Category: DNA-directed DNA polymerase]]
+[[Category: Ecoli]]
+[[Category: Large Structures]]
 [[Category: Kottur, J]]
 [[Category: Nair, D T]]

4q45

From Proteopedia

Revision as of 08:54, 24 April 2019

DNA Polymerase- damaged DNA complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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