2p66: Difference between revisions

Revision as of 12:27, 4 May 2008

Human DNA Polymerase beta complexed with tetrahydrofuran (abasic site) containing DNA

OverviewOverview

A large number of biochemical and genetic studies have demonstrated the involvement of DNA polymerase beta (Pol beta) in mammalian base excision repair (BER). Pol beta participates in BER sub-pathways by contributing gap filling DNA synthesis and lyase removal of the 5'-deoxyribose phosphate (dRP) group from the cleaved abasic site. To better understand the mechanism of the dRP lyase reaction at an atomic level, we determined a crystal structure of Pol beta complexed with 5'-phosphorylated abasic sugar analogs in nicked DNA. This DNA ligand represents a potential BER intermediate. The crystal structure reveals that the dRP group is bound in a non-catalytic binding site. The catalytic nucleophile in the dRP lyase reaction, Lys72, and all other potential secondary nucleophiles, are too far away to participate in nucleophilic attack on the C1' of the sugar. An approximate model of the dRP group in the expected catalytic binding site suggests that a rotation of 120 degrees about the dRP 3'-phosphate is required to position the epsilon-amino Lys72 close to the dRP C1'. This model also suggests that several other side chains are in position to facilitate the beta-elimination reaction. From results of mutational analysis of key residues in the dRP lyase active site, it appears that the substrate dRP can be stabilized in the observed non-catalytic binding conformation, hindering dRP lyase activity.

About this StructureAbout this Structure

2P66 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structural insight into the DNA polymerase beta deoxyribose phosphate lyase mechanism., Prasad R, Batra VK, Yang XP, Krahn JM, Pedersen LC, Beard WA, Wilson SH, DNA Repair (Amst). 2005 Dec 8;4(12):1347-57. Epub 2005 Sep 19. PMID:16172026 Page seeded by OCA on Sun May 4 12:27:27 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2p66.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2p66 |SIZE=350|CAPTION= <scene name='initialview01'>2p66</scene>, resolution 2.50&Aring;
+The line below this paragraph, containing "STRUCTURE_2p66", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=3DR:1&#39;,2&#39;-DIDEOXYRIBOFURANOSE-5&#39;-PHOSPHATE'>3DR</scene>, <scene name='pdbligand=DA:2&#39;-DEOXYADENOSINE-5&#39;-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2&#39;-DEOXYCYTIDINE-5&#39;-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2&#39;-DEOXYGUANOSINE-5&#39;-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5&#39;-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE= POLB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2p66|  PDB=2p66  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p66 OCA], [http://www.ebi.ac.uk/pdbsum/2p66 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2p66 RCSB]</span>
-}}
 '''Human DNA Polymerase beta complexed with tetrahydrofuran (abasic site) containing DNA'''
@@ Line 32: / Line 29: @@
 [[Category: Wilson, S H.]]
 [[Category: Yang, X P.]]
-[[Category: base excision repair]]
+[[Category: Base excision repair]]
-[[Category: dna repair]]
+[[Category: Dna repair]]
-[[Category: drp lyase]]
+[[Category: Drp lyase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 12:27:27 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:30:41 2008''