Probing the topography of HIV-1 nucleocapsid protein with the alkylating agent N-ethylmaleimide

The reactivity of specific Cys residues in the retroviral nucleocapsid protein was investigated by analyzing the topography of zinc fingers in different contexts using chemical probes. Experimental results showed that the conformation of free NCp7 inhibits the initial site of attack to Cys-49 and that the reactivity of thiols in full-length protein is different from that of the isolated zinc finger peptides. These results provide relevant parameters for the rational development of drugs for retroviral zinc fingers.