The Penultimate Tyrosine Residues are Critical for the Genotoxic Effect of Human Hemoglobin.

Autor:	Chakane S; Pure and Applied Biochemistry, Department of Chemistry, Lund University, 223 62, Lund, Sweden., Markad V; Department of Chemistry, Savitribai Phule Pune University, 411 007, Pune, India., Kodam K; Department of Chemistry, Savitribai Phule Pune University, 411 007, Pune, India., Bülow L; Pure and Applied Biochemistry, Department of Chemistry, Lund University, 223 62, Lund, Sweden. leif.bulow@tbiokem.lth.se.
Jazyk:	angličtina
Zdroj:	Advances in experimental medicine and biology [Adv Exp Med Biol] 2017; Vol. 977, pp. 351-357.
DOI:	10.1007/978-3-319-55231-6_46
Abstrakt:	Hemoglobin (Hb) is a potent oxidant outside the erythrocyte. The tyrosines α140 and β145 play an important role in the structure and function of Hb by forming switch and hinge contacts. These carboxy-terminal residues of the alpha and beta chains, respectively, were replaced to phenylalanine and several different methods were used to characterize the obtained mutants including a comet and plasmid DNA cleavage assay. It was observed that the genotoxic effect was 40% higher for αY140F compared with the wildtype, the βY145F and the double (αY140/β145F) mutants as determined by the comet assay. Cleavage of purified plasmid DNA after Hb application also revealed that the αY140F mutant showed 2-fold higher activity, while the βY145F and αY140/β145F mutants reduced the activity compared to wildtype Hb. This study clearly indicates that the penultimate tyrosines are involved in the genotoxicity of Hb.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu