Binding of chromium(VI) to histones: implications for chromium(VI)-induced genotoxicity.
The first evidence has been obtained for Cr(VI) (chromate) binding to isolated calf thymus (CT) histones under physiological conditions (pH 7.4, Cl(-) concentration 152 mM, 310 K). No significant Cr(VI) binding under the same conditions was observed for other extracellular and intracellular proteins, including albumin, apo-transferrin and G-actin, as well as for CT DNA. The mode of Cr(VI) binding to histones was studied by vibrational, electronic and X-ray absorption (X-ray absorption near-edge structure and X-ray absorption fine structure) spectroscopies and molecular mechanics calculations. A proposed binding mechanism includes electrostatic interactions of CrO(4) (2-) with protonated Lys and Arg residues of histones, as well as the formation of hydrogen bonds with the protein backbone. Similarly, Cr(VI) can bind to nuclear localization signals (typically, Lys- and Arg-rich fragments) of other nuclear proteins. Selective binding of Cr(VI) to newly synthesized nuclear proteins (including histones) in the cytoplasm is likely to be responsible for the active transport of Cr(VI) into the nuclei of living cells.
Levina
Aviva
A
Centre for Heavy Metals Research, and Centre for Structural Biology and Structural Chemistry, School of Chemistry, The University of Sydney, 2006 Sydney, NSW, Australia.
Harris
Hugh H
HH
Lay
Peter A
PA
D000818:Animals; D002274:Carcinogens, Environmental / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D002417:Cattle; D002857:Chromium / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D004247:DNA / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D015394:Molecular Structure; D009153:Mutagens / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism; D013057:Spectrum Analysis; D013950:Thymus Gland / Q000737:chemistry
D002274:Carcinogens, Environmental; D006657:Histones; D046911:Macromolecular Substances; D009153:Mutagens; D011506:Proteins; D002857:Chromium; C074702:chromium hexavalent ion; D004247:DNA