6jup

From Proteopedia

(Difference between revisions)

Current revision

Mutant PolIV-DNA incoming nucleotide complex

Structural highlights

6jup is a 6 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.44Å
Ligands:	,
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 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^[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
↑ Johnson MK, Kottur J, Nair DT. A polar filter in DNA polymerases prevents ribonucleotide incorporation. Nucleic Acids Res. 2019 Nov 18;47(20):10693-10705. doi: 10.1093/nar/gkz792. PMID:31544946 doi:http://dx.doi.org/10.1093/nar/gkz792

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/6jup"

Categories: Escherichia coli | Large Structures | Johnson MK | Nair DT

@@ Line 3: / Line 3: @@
 <StructureSection load='6jup' size='340' side='right'caption='[[6jup]], [[Resolution|resolution]] 2.44&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6jup]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JUP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JUP FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6jup]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JUP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JUP 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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.44&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dinB, dbh, dinB_1, dinB_2, A8C65_11955, A9R57_12995, ACU57_05495, AML35_26730, AUQ13_19210, BANRA_02184, BANRA_03427, BET08_31995, BHS87_01175, BJJ90_21040, BMT91_15875, BUE81_28425, C5N07_13800, C9E25_22940, CA593_02435, CRM83_14635, CV83915_01335, CWS33_23695, D0X26_15110, D2185_22400, D3O91_23685, D3Y67_06560, D9D20_20085, D9D69_23735, D9E22_12045, D9F57_19765, D9H66_20200, D9H68_19465, D9I18_13635, D9J11_18290, D9J11_27145, D9J44_21795, DNQ41_05075, DTL43_23485, EAI44_14085, EAI52_15440, EC1094V2_3597, EC3234A_186c00130, EC3426_01008, EC382_20155, EC382_27145, ECTO6_03825, EEP23_17825, EFV02_01800, EFV04_12320, EFV12_23405, EFV17_17010, ERS085365_04420, ERS139211_04423, ERS150873_03537, HW43_04975, NCTC10865_04963, NCTC11022_04998, NCTC11126_03759, NCTC13148_06847, NCTC13462_02133, NCTC8985_02971, NCTC9037_04075, NCTC9045_04586, NCTC9058_02901, NCTC9062_04328, NCTC9073_03243, NCTC9117_04957, NCTC9706_01202, RK56_027425, SAMEA3472043_03017, SAMEA3472047_03125, SAMEA3472070_01946, SAMEA3484427_04943, SAMEA3484429_04916, SAMEA3752557_00095, SAMEA3752559_04620, SAMEA3753300_00345, SK85_00262, WQ89_22460, WR15_21380 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=6jup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jup OCA], [https://pdbe.org/6jup PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jup RCSB], [https://www.ebi.ac.uk/pdbsum/6jup PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jup ProSAT]</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=6jup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jup OCA], [http://pdbe.org/6jup PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jup RCSB], [http://www.ebi.ac.uk/pdbsum/6jup PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jup ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/W8STT9_ECOLX W8STT9_ECOLX]] 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.[SAAS:SAAS00538441]  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.[HAMAP-Rule:MF_01113]
+[https://www.uniprot.org/uniprot/DPO4_ECOLI 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.<ref>PMID:9391106</ref> <ref>PMID:11080171</ref> <ref>PMID:11463382</ref> <ref>PMID:11751576</ref> <ref>PMID:12060704</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 19: @@
 </div>
 <div class="pdbe-citations 6jup" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Bacillus coli migula 1895]]
+[[Category: Escherichia coli]]
-[[Category: DNA-directed DNA polymerase]]
 [[Category: Large Structures]]
-[[Category: Johnson, M K]]
+[[Category: Johnson MK]]
-[[Category: Nair, D T]]
+[[Category: Nair DT]]
-[[Category: Dna polymerase]]
-[[Category: Replication]]
-[[Category: Replication-dna complex]]

6jup

From Proteopedia

Current revision

Mutant PolIV-DNA incoming nucleotide complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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