4rt2: Difference between revisions

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'''Unreleased structure'''


The entry 4rt2 is ON HOLD
==Ternary complex crystal structure of DNA polymerase Beta with (alpha,beta)-CH2-(beta,gamma)-NH-dTTP==
<StructureSection load='4rt2' size='340' side='right'caption='[[4rt2]], [[Resolution|resolution]] 1.92&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4rt2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RT2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RT2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.92&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=N6T:2-DEOXY-5-O-[(S)-HYDROXY{[(S)-HYDROXY(PHOSPHONOAMINO)PHOSPHORYL]METHYL}PHOSPHORYL]-3,4-DIHYDROTHYMIDINE'>N6T</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=4rt2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rt2 OCA], [https://pdbe.org/4rt2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rt2 RCSB], [https://www.ebi.ac.uk/pdbsum/4rt2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rt2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://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.


Authors: Batra, V.K., Wilson, S.H.
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>


Description: Ternary complex crystal structure of DNA polymerase Beta with (alpha,beta)-CH2-(beta,gamma)-NH-dTTP
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4rt2" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Batra VK]]
[[Category: Wilson SH]]

Latest revision as of 20:55, 20 September 2023

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

Structural highlights

4rt2 is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.92Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

See Also

References

  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:http://dx.doi.org/10.1021/acs.orglett.5b00799

4rt2, resolution 1.92Å

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