3MDC

DNA polymerase lambda in complex with dFdCTP

Summary for 3MDC

• Entry DOI: 10.2210/pdb3mdc/pdb
• Related: 3MDA
• Descriptor: DNA polymerase lambda, DNA (5'-D(*CP*GP*GP*CP*GP*GP*TP*AP*CP*TP*G)-3'), DNA (5'-D(*CP*AP*GP*TP*AP*C)-3'), ... (8 entities in total)
• Functional Keywords: protein-dna complex, lyase, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q9UGP5
• Total number of polymer chains: 4
• Total formula weight: 43424.52

Authors

Garcia-Diaz, M.,Murray, M.,Kunkel, T.,Chou, K.M. (deposition date: 2010-03-30, release date: 2010-04-28, Last modification date: 2024-02-21)

Primary citation

Garcia-Diaz, M.,Murray, M.S.,Kunkel, T.A.,Chou, K.M.
Interaction between DNA Polymerase lambda and anticancer nucleoside analogs.
J.Biol.Chem., 285:16874-16879, 2010

PubMed Abstract: The anticancer activity of cytarabine (AraC) and gemcitabine (dFdC) is thought to result from chain termination after incorporation into DNA. To investigate their incorporation into DNA at atomic level resolution, we present crystal structures of human DNA polymerase lambda (Pol lambda) bound to gapped DNA and containing either AraC or dFdC paired opposite template dG. These structures reveal that AraC and dFdC can bind within the nascent base pair binding pocket of Pol lambda. Although the conformation of the ribose of AraCTP is similar to that of normal dCTP, the conformation of dFdCTP is significantly different. Consistent with these structures, Pol lambda efficiently incorporates AraCTP but not dFdCTP. The data are consistent with the possibility that Pol lambda could modulate the cytotoxic effect of AraC.

PubMed: 20348107
DOI: 10.1074/jbc.M109.094391

Experimental method

X-RAY DIFFRACTION (1.999 Å)