The transcription regulator PbrR691, one of the MerR family proteins, shows extremely high sensitivity and selectivity toward Pb(II) in Ralstonia metallidurans CH34. Here, we present the crystal structure of PbrR691 in complex with Pb(II) at 2.0 Å resolution. The Pb(II) coordinates with three conserved cysteines and adopts a unique trigonal-pyramidal (hemidirected) geometry. To our knowledge, the PbrR691-Pb(II) structure provides the first three-dimensional visualization of a functional hemidirected lead(II) thiolate coordinate geometry in a protein.

Cisplatin, one of the most effective anticancer drugs, is a DNA-damaging agent that induces cell death primarily by apoptosis. For many years, HMGB1 has been known to be a recognition protein for cisplatin–DNA lesions. Here, an application of a biomolecular probe based on a peptide–oligonucleotide conjugate is presented as a novel method for investigating this recognition process in vivo. Proteins known to be involved in the recognition of cisplatin-damaged DNA were pulled down and identified, including members of the HMGB family and a number of other proteins. Interestingly, at least 4 subforms of HMGB1 bind to cisplatin–DNA adducts. These proteins were further identified as post-translationally acetylated or phosphorylated forms of HMGB1. These results provide a rich pool of protein candidates whose roles in the mechanism of action of platinum drugs should be explored. These newly discovered molecular components of the DNA damage signalling cascade could serve as novel links between the initial cell responses to DNA damage and the downstream apoptotic or DNA repair pathways.

In order to systematically investigate the influence of carrier ligands on the interaction of Pt–DNA adducts with damage recognition proteins, a series of DNA probes containing 1,2-GG platinum compound crosslinks using cisplatin, oxaliplatin, (S,S-DACH)PtCl2 and (cis-1,4-DACH)PtCl2 (kiteplatin) has been constructed. These complexes share similar DNA binding properties although they exhibit quite different cytotoxicity. It is revealed that HMGB1 (high-mobility group protein B1) was the most commonly found protein that recognizes all Pt(II)-DNA probes and prefers cisplatin–DNA probes more than the others. Interestingly, an important component of the replication protein A complex, RPA2, was found to bind to kiteplatin much more tightly than other proteins. These results may be important for the interpretation of the roles of carrier ligands in platinum(II)-based anticancer complexes.

Cisplatin, one of the most effective anticancer drugs, is a DNA-damaging agent that induces cell death primarily by apoptosis. For many years, HMGB1 has been known to be a recognition protein for cisplatin–DNA lesions. Here, an application of a biomolecular probe based on a peptide–oligonucleotide conjugate is presented as a novel method for investigating this recognition process in vivo. Proteins known to be involved in the recognition of cisplatin-damaged DNA were pulled down and identified, including members of the HMGB family and a number of other proteins. Interestingly, at least 4 subforms of HMGB1 bind to cisplatin–DNA adducts. These proteins were further identified as post-translationally acetylated or phosphorylated forms of HMGB1. These results provide a rich pool of protein candidates whose roles in the mechanism of action of platinum drugs should be explored. These newly discovered molecular components of the DNA damage signalling cascade could serve as novel links between the initial cell responses to DNA damage and the downstream apoptotic or DNA repair pathways.

In order to systematically investigate the influence of carrier ligands on the interaction of Pt–DNA adducts with damage recognition proteins, a series of DNA probes containing 1,2-GG platinum compound crosslinks using cisplatin, oxaliplatin, (S,S-DACH)PtCl2 and (cis-1,4-DACH)PtCl2 (kiteplatin) has been constructed. These complexes share similar DNA binding properties although they exhibit quite different cytotoxicity. It is revealed that HMGB1 (high-mobility group protein B1) was the most commonly found protein that recognizes all Pt(II)-DNA probes and prefers cisplatin–DNA probes more than the others. Interestingly, an important component of the replication protein A complex, RPA2, was found to bind to kiteplatin much more tightly than other proteins. These results may be important for the interpretation of the roles of carrier ligands in platinum(II)-based anticancer complexes.