1S0M

Crystal structure of a Benzo[a]pyrene Diol Epoxide adduct in a ternary complex with a DNA polymerase

Summary for 1S0M

• Entry DOI: 10.2210/pdb1s0m/pdb
• Related: 1JX4 1RYR 1RYS 1S0N 1S0O 1S10
• Descriptor: 5'-D(*GP*GP*GP*GP*GP*AP*AP*GP*GP*AP*TP*TP*T)-3', 5'-D(P*AP*TP*AP*AP*AP*TP*CP*CP*TP*TP*CP*CP*CP*CP*CP*A)-3', DNA polymerase IV, ... (8 entities in total)
• Functional Keywords: benzo pyrene, carcinogen, lesion bypass, polymerase, transferase-dna complex, transferase/dna
• Biological source: Sulfolobus solfataricus
• Total number of polymer chains: 6
• Total formula weight: 100159.25

Authors

Ling, H.,Sayer, J.M.,Boudsocq, F.,Plosky, B.S.,Woodgate, R.,Yang, W. (deposition date: 2003-12-31, release date: 2004-03-30, Last modification date: 2023-08-23)

Primary citation

Ling, H.,Sayer, J.M.,Plosky, B.S.,Yagi, H.,Boudsocq, F.,Woodgate, R.,Jerina, D.M.,Yang, W.
Crystal structure of a benzo[a]pyrene diol epoxide adduct in a ternary complex with a DNA polymerase.
Proc.Natl.Acad.Sci.USA, 101:2265-2269, 2004

PubMed Abstract: The first occupation-associated cancers to be recognized were the sooty warts (cancers of the scrotum) suffered by chimney sweeps in 18th century England. In the 19th century, high incidences of skin cancers were noted among fuel industry workers. By the early 20th century, malignant skin tumors were produced in laboratory animals by repeatedly painting them with coal tar. The culprit in coal tar that induces cancer was finally isolated in 1933 and determined to be benzo[a]pyrene (BP), a polycyclic aromatic hydrocarbon. A residue of fuel and tobacco combustion and frequently ingested by humans, BP is metabolized in mammals to benzo[a]pyrene diol epoxide (BPDE), which forms covalent DNA adducts and induces tumor growth. In the 70 yr since its isolation, BP has been the most studied carcinogen. Yet, there has been no crystal structure of a BPDE DNA adduct. We report here the crystal structure of a BPDE-adenine adduct base-paired with thymine at a template-primer junction and complexed with the lesion-bypass DNA polymerase Dpo4 and an incoming nucleotide. Two conformations of the BPDE, one intercalated between base pairs and another solvent-exposed in the major groove, are observed. The latter conformation, which can be stabilized by organic solvents that reduce the dielectric constant, seems more favorable for DNA replication by Dpo4. These structures also suggest a mechanism by which mutations are generated during replication of DNA containing BPDE adducts.

PubMed: 14982998
DOI: 10.1073/pnas.0308332100

Experimental method

X-RAY DIFFRACTION (2.7 Å)