View source for 2pfp

[[Image:2pfp.gif|left|200px]]

 {{Structure
|PDB= 2pfp |SIZE=350|CAPTION= <scene name='initialview01'>2pfp</scene>, resolution 2.100&Aring;
|SITE= 
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> and <scene name='pdbligand=DCP:2'-DEOXYCYTIDINE-5'-TRIPHOSPHATE'>DCP</scene>
|ACTIVITY= 
|GENE= POLL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
}}

'''DNA Polymerase lambda in complex with DNA and dCTP'''


==Overview==
The incorporation of dNMPs into DNA by polymerases involves a phosphoryl transfer reaction hypothesized to require two divalent metal ions. Here we investigate this hypothesis using as a model human DNA polymerase lambda (Pol lambda), an enzyme suggested to be activated in vivo by manganese. We report the crystal structures of four complexes of human Pol lambda. In a 1.9 A structure of Pol lambda containing a 3'-OH and the non-hydrolyzable analog dUpnpp, a non-catalytic Na+ ion occupies the site for metal A and the ribose of the primer-terminal nucleotide is found in a conformation that positions the acceptor 3'-OH out of line with the alpha-phosphate and the bridging oxygen of the pyrophosphate leaving group. Soaking this crystal in MnCl2 yielded a 2.0 A structure with Mn2+ occupying the site for metal A. In the presence of Mn2+, the conformation of the ribose is C3'-endo and the 3'-oxygen is in line with the leaving oxygen, at a distance from the phosphorus atom of the alpha-phosphate (3.69 A) consistent with and supporting a catalytic mechanism involving two divalent metal ions. Finally, soaking with MnCl2 converted a pre-catalytic Pol lambda/Na+ complex with unreacted dCTP in the active site into a product complex via catalysis in the crystal. These data provide pre- and post-transition state information and outline in a single crystal the pathway for the phosphoryl transfer reaction carried out by DNA polymerases.

==About this Structure==
2PFP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PFP OCA]. 

==Reference==
Role of the catalytic metal during polymerization by DNA polymerase lambda., Garcia-Diaz M, Bebenek K, Krahn JM, Pedersen LC, Kunkel TA, DNA Repair (Amst). 2007 Sep 1;6(9):1333-40. Epub 2007 May 1. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17475573 17475573]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Bebenek, K.]]
[[Category: Garcia-Diaz, M.]]
[[Category: Krahn, J M.]]
[[Category: Kunkel, T A.]]
[[Category: Pedersen, L C.]]
[[Category: DCP]]
[[Category: MG]]
[[Category: NA]]
[[Category: dna polymerase]]
[[Category: dna repair]]
[[Category: manganese]]
[[Category: phosphoryl transfer reaction]]

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