PDBsum entry 3mda

Lyase,transferase/DNA

PDB id: 3mda

Contents

Protein chain

325 a.a. *

DNA/RNA

Ligands

PPV

Metals

_MG

_NA ×2

Waters ×290

* Residue conservation analysis

PDB id:

3mda

Name:

Lyase,transferase/DNA

Title:

DNA polymerase lambda in complex with arac

Structure:

DNA polymerase lambda. Chain: a. Synonym: pol lambda, DNA polymerase kappa, DNA polymerase beta-2, pol beta2. Engineered: yes. DNA (5'-d( Cp Gp Gp Cp Gp Gp Tp Ap Cp Tp G)-3'). Chain: t. Engineered: yes. DNA (5'-d( Cp Ap Gp Tp Ap Cp (Car))-3').

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: poll. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the DNA fragment is chemically synthesized.. Other_details: the DNA fragment is chemically synthesized.

Resolution:

2.03Å R-factor: 0.200 R-free: 0.259

Authors:

M.Garcia-Diaz,M.Murray,T.Kunkel,K.M.Chou

Key ref:

M.Garcia-Diaz et al. (2010). Interaction between DNA Polymerase lambda and anticancer nucleoside analogs. J Biol Chem, 285, 16874-16879. PubMed id: 20348107

Date:

30-Mar-10 Release date: 28-Apr-10

Protein chain

Q9UGP5  (DPOLL_HUMAN) -  DNA polymerase lambda from Homo sapiens

Seq: 575 a.a.

Struc: 325 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DNA/RNA chains

C-G-G-C-G-G-T-A-C-T-G 11 bases

C-A-G-T-A-C-CAR 7 bases

G-C-C-G 4 bases

Enzyme reactions

• Enzyme class 2: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate

DNA(n) + 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) (Bound ligand (Het Group name = PPV) corresponds exactly) + diphosphate

• Enzyme class 3: E.C.4.2.99.- - ?????

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

J Biol Chem 285:16874-16879 (2010)

PubMed id: 20348107

Interaction between DNA Polymerase lambda and anticancer nucleoside analogs.

M.Garcia-Diaz, M.S.Murray, T.A.Kunkel, K.M.Chou.

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.