Structure of Photolyase

Photolyases are monomeric proteins of 450—550 amino acids and two noncovalently bound cofactors (Johnson et al, 1988 Joms et al, 1984). One of the cofactors is always FAD. The other cofactor, which is also called the second chromophore, is methenyltetrahydrofolate (MTHF) in the majority of photolyases and 8-hydroxy-7,8-didemethyl-5-deazariboflavm (8-HDF) in a limited number of species (some archaea, Anacystis nidulans, and some ferns that synthesize this cofactor) (Eker et al., 1988, 1990 Johnson et al, 1988 Kiener et al, 1989 Malhotra et al, 1992). 

Grystal structures of photo lyases from E. coli (Park ei al., 1995), A. nidulans (Tamada et al, 1997), and Thermus thermophilus (Komori et al, 2001) have been solved. Although they possess different second chromo-phores E. coli photolyase has MTHF and the latter two contain 8-HDF), and the level of overall sequence homology among the three enzymes is only about 25% sequence identity, the structures of all three are remarkably similar. Here, the structure of E. coli photolyase will be presented and the minor differences of the other two photolyases from this structure will be briefly mentioned. 

The structure of A. nidulans photolyase is very similar to that of the E. coU enzyme, with one important exception the 8-HDF photoantenna is deeply buried into the interdomain cleft and the center-to-center distance between the two chromophores is 17.5 A. However, the planes of the two chromophores are nearly parallel, allowing for more efficient energy transfer from the second chromophore to FAD, even though they are farther apart than the two chromophores in E. coU photolyase (Rim et al., 1992 Tamada et al., 1997). The T. photolyase has a shorter interdo- 

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Fig. 2. Structures of photolyase/cryptochrome cofactors. All photolyases and cryptochromes contain FAD, and all either contain or are thought to contain 5,10-methenyltetrahydrofolate (MTHF) or 8-hydroxy-7,8-didemethyl-5-deazariboflavin (8-HDF) as the second chromophore.

Molecular modeling of mammalian cryptochromes on the structure of photolyase indicates conservation of the chromophore-binding regions, the DNA binding groove, as weU as the damage-binding pocket. However, the functional implications of these structural features for cryptochrome function in circadian photoreception are unknown. The major difference between cryptochrome and photolyase Hes in the presence of an extended C-terminal tail in cryptochrome, which is absent in photolyase. Based on... 

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