4rt3: Difference between revisions

Revision as of 12:12, 1 July 2015

Ternary complex crystal structure of DNA polymerase Beta with (alpha, beta)-NH-(beta,gamma)-CH2-dTTP

Structural highlights

4rt3 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	C6T, CL, MG, NA
NonStd Res:	DOC
Related:	4rt2
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[DPOLB_HUMAN] Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Novel alpha,beta-CH2 and beta,gamma-NH (1a) or alpha,beta-NH and beta,gamma-CH2 (1b) "Met-Im" dTTPs were synthesized via monodemethylation of triethyl-dimethyl phosphorimido-bisphosphonate synthons (4a, 4b), formed via a base-induced [1,3]-rearrangement of precursors (3a, 3b) in a reaction with dimethyl or diethyl phosphochloridate. Anomerization during final bromotrimethylsilane (BTMS) deprotection after Mitsunobu conjugation with dT was avoided by microwave conditions. 1a was 9-fold more potent in inhibiting DNA polymerase beta, attributed to an NH-group interaction with R183 in the active site.

Two Scaffolds from Two Flips: (alpha,beta)/(beta,gamma) CH2/NH "Met-Im" Analogues of dTTP.,Kadina AP, Kashemirov BA, Oertell K, Batra VK, Wilson SH, Goodman MF, McKenna CE Org Lett. 2015 Jun 5;17(11):2586-9. doi: 10.1021/acs.orglett.5b00799. Epub 2015, May 13. PMID:25970636^[5]

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

References

↑ Bennett RA, Wilson DM 3rd, Wong D, Demple B. Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7166-9. PMID:9207062
↑ Matsumoto Y, Kim K, Katz DS, Feng JA. Catalytic center of DNA polymerase beta for excision of deoxyribose phosphate groups. Biochemistry. 1998 May 5;37(18):6456-64. PMID:9572863 doi:10.1021/bi9727545
↑ DeMott MS, Beyret E, Wong D, Bales BC, Hwang JT, Greenberg MM, Demple B. Covalent trapping of human DNA polymerase beta by the oxidative DNA lesion 2-deoxyribonolactone. J Biol Chem. 2002 Mar 8;277(10):7637-40. Epub 2002 Jan 22. PMID:11805079 doi:10.1074/jbc.C100577200
↑ Parsons JL, Dianova II, Khoronenkova SV, Edelmann MJ, Kessler BM, Dianov GL. USP47 is a deubiquitylating enzyme that regulates base excision repair by controlling steady-state levels of DNA polymerase beta. Mol Cell. 2011 Mar 4;41(5):609-15. doi: 10.1016/j.molcel.2011.02.016. PMID:21362556 doi:10.1016/j.molcel.2011.02.016
↑ Kadina AP, Kashemirov BA, Oertell K, Batra VK, Wilson SH, Goodman MF, McKenna CE. Two Scaffolds from Two Flips: (alpha,beta)/(beta,gamma) CH2/NH "Met-Im" Analogues of dTTP. Org Lett. 2015 Jun 5;17(11):2586-9. doi: 10.1021/acs.orglett.5b00799. Epub 2015, May 13. PMID:25970636 doi:https://dx.doi.org/10.1021/acs.orglett.5b00799

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Bennett RA, Wilson DM 3rd, Wong D, Demple B. Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7166-9. PMID:9207062

[2] Matsumoto Y, Kim K, Katz DS, Feng JA. Catalytic center of DNA polymerase beta for excision of deoxyribose phosphate groups. Biochemistry. 1998 May 5;37(18):6456-64. PMID:9572863 doi:10.1021/bi9727545

[3] DeMott MS, Beyret E, Wong D, Bales BC, Hwang JT, Greenberg MM, Demple B. Covalent trapping of human DNA polymerase beta by the oxidative DNA lesion 2-deoxyribonolactone. J Biol Chem. 2002 Mar 8;277(10):7637-40. Epub 2002 Jan 22. PMID:11805079 doi:10.1074/jbc.C100577200

[4] Parsons JL, Dianova II, Khoronenkova SV, Edelmann MJ, Kessler BM, Dianov GL. USP47 is a deubiquitylating enzyme that regulates base excision repair by controlling steady-state levels of DNA polymerase beta. Mol Cell. 2011 Mar 4;41(5):609-15. doi: 10.1016/j.molcel.2011.02.016. PMID:21362556 doi:10.1016/j.molcel.2011.02.016

[5] Kadina AP, Kashemirov BA, Oertell K, Batra VK, Wilson SH, Goodman MF, McKenna CE. Two Scaffolds from Two Flips: (alpha,beta)/(beta,gamma) CH2/NH "Met-Im" Analogues of dTTP. Org Lett. 2015 Jun 5;17(11):2586-9. doi: 10.1021/acs.orglett.5b00799. Epub 2015, May 13. PMID:25970636 doi:https://dx.doi.org/10.1021/acs.orglett.5b00799

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Ternary complex crystal structure of DNA polymerase Beta with (alpha, beta)-NH-(beta,gamma)-CH2-dTTP==
+<StructureSection load='4rt3' size='340' side='right' caption='[[4rt3]], [[Resolution|resolution]] 1.92&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4rt3]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RT3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RT3 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C6T:2-DEOXY-5-O-[(S)-HYDROXY{[(R)-HYDROXY(PHOSPHONOMETHYL)PHOSPHORYL]AMINO}PHOSPHORYL]-3,4-DIHYDROTHYMIDINE'>C6T</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4rt2|4rt2]]</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=4rt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rt3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rt3 RCSB], [http://www.ebi.ac.uk/pdbsum/4rt3 PDBsum]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/DPOLB_HUMAN DPOLB_HUMAN]] Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.<ref>PMID:9207062</ref> <ref>PMID:9572863</ref> <ref>PMID:11805079</ref> <ref>PMID:21362556</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Novel alpha,beta-CH2 and beta,gamma-NH (1a) or alpha,beta-NH and beta,gamma-CH2 (1b) "Met-Im" dTTPs were synthesized via monodemethylation of triethyl-dimethyl phosphorimido-bisphosphonate synthons (4a, 4b), formed via a base-induced [1,3]-rearrangement of precursors (3a, 3b) in a reaction with dimethyl or diethyl phosphochloridate. Anomerization during final bromotrimethylsilane (BTMS) deprotection after Mitsunobu conjugation with dT was avoided by microwave conditions. 1a was 9-fold more potent in inhibiting DNA polymerase beta, attributed to an NH-group interaction with R183 in the active site.
-The entry 4rt3 is ON HOLD  until Paper Publication
+Two Scaffolds from Two Flips: (alpha,beta)/(beta,gamma) CH2/NH "Met-Im" Analogues of dTTP.,Kadina AP, Kashemirov BA, Oertell K, Batra VK, Wilson SH, Goodman MF, McKenna CE Org Lett. 2015 Jun 5;17(11):2586-9. doi: 10.1021/acs.orglett.5b00799. Epub 2015, May 13. PMID:25970636<ref>PMID:25970636</ref>
-Authors: Batra, V.K., Wilson, S.H.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Ternary complex crystal structure of DNA polymerase Beta with (alpha, beta)-NH-(beta,gamma)-CH2-dTTP
+== References ==
-[[Category: Unreleased Structures]]
+<references/>
-[[Category: Wilson, S.H]]
+__TOC__
-[[Category: Batra, V.K]]
+</StructureSection>
+[[Category: Batra, V K]]
+[[Category: Wilson, S H]]
+[[Category: Dna polymerase beta]]
+[[Category: Ternary complex]]
+[[Category: Transferase-dna complex]]

4rt3: Difference between revisions

Revision as of 12:12, 1 July 2015

Ternary complex crystal structure of DNA polymerase Beta with (alpha, beta)-NH-(beta,gamma)-CH2-dTTP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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