2jej
From Proteopedia
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- | [[ | + | ==THE MOLECULAR BASIS OF SELECTIVITY OF NUCLEOSIDE TRIPHOSPHATE INCORPORATION OPPOSITE O6-BENZYLGUANINE BY SULFOLOBUS SOLFATARICUS DNA POLYMERASE IV: STEADY-STATE AND PRE-STEADY-STATE KINETICS AND X-RAY CRYSTALLOGRAPHY OF CORRECT AND INCORRECT PAIRING== |
+ | <StructureSection load='2jej' size='340' side='right' caption='[[2jej]], [[Resolution|resolution]] 1.86Å' scene=''> | ||
+ | == Structural highlights == | ||
+ | <table><tr><td colspan='2'>[[2jej]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Sulfolobus_solfataricus Sulfolobus solfataricus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JEJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JEJ FirstGlance]. <br> | ||
+ | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DGT:2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>DGT</scene><br> | ||
+ | <tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=BZG:6-(BENZYLOXY)-9-(2-DEOXY-5-O-PHOSPHONO-BETA-D-ERYTHRO-PENTOFURANOSYL)-9H-PURIN-2-AMINE'>BZG</scene></td></tr> | ||
+ | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1jx4|1jx4]], [[1jxl|1jxl]], [[1n48|1n48]], [[1n56|1n56]], [[1ryr|1ryr]], [[1rys|1rys]], [[1s0m|1s0m]], [[1s0n|1s0n]], [[1s0o|1s0o]], [[1s10|1s10]], [[1s97|1s97]], [[1s9f|1s9f]], [[2ago|2ago]], [[2agp|2agp]], [[2agq|2agq]], [[2asd|2asd]], [[2asj|2asj]], [[2asl|2asl]], [[2atl|2atl]], [[2au0|2au0]], [[2bq3|2bq3]], [[2bqr|2bqr]], [[2bqu|2bqu]], [[2br0|2br0]], [[2c22|2c22]], [[2c28|2c28]], [[2c2d|2c2d]], [[2c2e|2c2e]], [[2c2r|2c2r]], [[2j6s|2j6s]], [[2j6t|2j6t]], [[2j6u|2j6u]], [[2jef|2jef]], [[2jeg|2jeg]], [[2jei|2jei]]</td></tr> | ||
+ | <tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2jej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jej OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2jej RCSB], [http://www.ebi.ac.uk/pdbsum/2jej PDBsum]</span></td></tr> | ||
+ | <table> | ||
+ | == Evolutionary Conservation == | ||
+ | [[Image:Consurf_key_small.gif|200px|right]] | ||
+ | Check<jmol> | ||
+ | <jmolCheckbox> | ||
+ | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/je/2jej_consurf.spt"</scriptWhenChecked> | ||
+ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
+ | <text>to colour the structure by Evolutionary Conservation</text> | ||
+ | </jmolCheckbox> | ||
+ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
+ | <div style="clear:both"></div> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | Previous work has shown that Sulfolobus solfataricus DNA polymerase Dpo4-catalyzed bypass of O(6)-methylguanine (O(6)-MeG) proceeds largely in an accurate but inefficient manner with a "wobble" base pairing between C and O(6)-MeG (Eoff, R. L., Irimia, A., Egli, M., and Guengerich, F. P. (2007) J. Biol. Chem. 282, 1456-1467). We considered here the bulky lesion O(6)-benzylguanine (O(6)-BzG) in DNA and catalysis by Dpo4. Mass spectrometry analysis of polymerization products revealed that the enzyme bypasses and extends across from O(6)-BzG, with C the major product ( approximately 70%) and some T and A ( approximately 15% each) incorporated opposite the lesion. Steady-state kinetic parameters indicated that Dpo4 was 7-, 5-, and 27-fold more efficient at C incorporation opposite O(6)-BzG than T, A, or G, respectively. In transient state kinetic analysis, the catalytic efficiency was decreased 62-fold for C incorporation opposite O(6)-BzG relative to unmodified DNA. Crystal structures reveal wobble pairing between C and O(6)-BzG. Pseudo-"Watson-Crick" pairing was observed between T and O(6)-BzG. Two other structures illustrate a possible mechanism for the accommodation of a +1 frameshift in the Dpo4 active site. The overall effect of O(6)-BzG is to decrease the efficiency of bypass by roughly an order of magnitude in every case except correct bypass, where the effect is not as pronounced. By comparison, Dpo4 is more accurate but no more efficient than model replicative polymerases, such as bacteriophage T7(-) DNA polymerase and human immunodeficiency virus-1 reverse transcriptase in the polymerization past O(6)-MeG and O(6)-BzG. | ||
- | + | Molecular basis of selectivity of nucleoside triphosphate incorporation opposite O6-benzylguanine by sulfolobus solfataricus DNA polymerase Dpo4: steady-state and pre-steady-state kinetics and x-ray crystallography of correct and incorrect pairing.,Eoff RL, Angel KC, Egli M, Guengerich FP J Biol Chem. 2007 May 4;282(18):13573-84. Epub 2007 Mar 3. PMID:17337730<ref>PMID:17337730</ref> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | + | </div> | |
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==See Also== | ==See Also== | ||
*[[DNA polymerase|DNA polymerase]] | *[[DNA polymerase|DNA polymerase]] | ||
- | + | == References == | |
- | == | + | <references/> |
- | < | + | __TOC__ |
+ | </StructureSection> | ||
[[Category: DNA-directed DNA polymerase]] | [[Category: DNA-directed DNA polymerase]] | ||
[[Category: Sulfolobus solfataricus]] | [[Category: Sulfolobus solfataricus]] |
Revision as of 02:50, 29 September 2014
THE MOLECULAR BASIS OF SELECTIVITY OF NUCLEOSIDE TRIPHOSPHATE INCORPORATION OPPOSITE O6-BENZYLGUANINE BY SULFOLOBUS SOLFATARICUS DNA POLYMERASE IV: STEADY-STATE AND PRE-STEADY-STATE KINETICS AND X-RAY CRYSTALLOGRAPHY OF CORRECT AND INCORRECT PAIRING
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Categories: DNA-directed DNA polymerase | Sulfolobus solfataricus | Angel, K C. | Egli, M. | Eoff, R L. | Guengerich, F P. | Kosekov, I D. | 06-benzylguanine | Alkylating agent | Dna damage | Dna repair | Dna replication | Dna-binding | Dna-directed dna polymerase | Dpo4 | Magnesium | Metal-binding | Mutator protein | Nucleotidyltransferase | Polymerase | Transferase | Translesion synthesis