During replication of human immunodeficiency virus type 1 (HIV-1), virus-encoded reverse transcriptase (RT) catalyses the conversion of the single-stranded RNA genome to a double-stranded DNA genome. HIV-1 RT functions as a heterodimer, comprising a 66 and a 51 kDa subunit (p66 and p51, respectively). The p66 subunit folds into two distinct domains : a typical polymerase domain and a connected RNase H domain. The second subunit, p51, is a copy of p66 in which the 15 kDa RNase H carboxy-terminal segment has been cleaved by the HIV-1 protease and which lacks a functional nucleic acid-binding cleft. The polymerase domain, p66, consists of four subdomains, which are, by analogy with parts of a right hand, referred to as 'fingers ', 'palm ', ' thumb ' or ' connection '. These subdomains constitute the functional nucleic acid-binding cleft.