The SCAN domain is described as a highly conserved, leucine-rich motif of approximately 60 amino acids found at the amino-terminal end of zinc finger transcription factors. Although no specific biological function has been attributed to the SCAN domain, its predicted amphipathic secondary structure led to the suggestion that this domain may mediate protein-protein associations. The SCAN or leucine-rich domain, originally identified by its homology with similar elements in several zinc finger transcription factors, consists of approximately 60 amino acids and is rich in leucine and glutamic acid residues (1). Most SCAN domain sequences are linked to Cys 2 -His 2 zinc finger motifs through their carboxyl-terminal end. Although the function of the SCAN domain has not yet been elucidated, the predicted amphipathic structure of the domain led to the suggestion that SCAN box elements have the capacity to interact with other proteins, in particular with components of the transcriptional machinery (1).The zinc finger protein ZNF202 1 is expressed in two common splice variants, here referred to as m1 and m3 (2). Whereas the m1-splice form encodes a full-length protein of 648 amino acids with a SCAN box, a KRAB repression domain, and eight Cys 2 -His 2 zinc finger motifs, the 133 amino acid product of the m3-splice form encompasses only the SCAN domain.2 These splice forms are conserved in the murine ZNF202 homolog, suggesting that the SCAN motif itself is an independent functional domain.3

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Hydroperoxide-induced tyrosyl radicals are putative intermediates in cyclooxygenase catalysis by prostaglandin H synthase (PGHS)-1 and -2. Rapid-freeze EPR and stopped-flow were used to characterize tyrosyl radical kinetics in PGHS-1 and -2 reacted with ethyl hydrogen peroxide. In PGHS-1, a wide doublet tyrosyl radical (34 -35 G) was formed by 4 ms, followed by transition to a wide singlet (33-34 G); changes in total radical intensity paralleled those of Intermediate II absorbance during both formation and decay phases. In PGHS-2, some wide doublet (30 G) was present at early time points, but transition to wide singlet (29 G) was complete by 50 ms. In contrast to PGHS-1, only the formation kinetics of the PGHS-2 tyrosyl radical matched the Intermediate II absorbance kinetics. Indomethacin-treated PGHS-1 and nimesulide-treated PGHS-2 rapidly formed narrow singlet EPR (25-26 G in PGHS-1; 21 G in PGHS-2), and the same line shapes persisted throughout the reactions. Radical intensity paralleled Intermediate II absorbance throughout the indomethacin-treated PGHS-1 reaction. For nimesulide-treated PGHS-2, radical formed in concert with Intermediate II, but later persisted while Intermediate II relaxed. These results substantiate the kinetic competence of a tyrosyl radical as the catalytic intermediate for both PGHS isoforms and also indicate that the heme redox state becomes uncoupled from the tyrosyl radical in PGHS-2.

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