Evolution of the aldose reductase-related gecko eye lens protein rhoB-crystallin: a sheep in wolf's clothing.
rhoB-crystallin (AJ245805) is a major protein component (20%) in the eye lens of the gecko Lepidodactylus lugubris. Limited peptide sequence analysis earlier revealed that it belongs to the aldo-keto reductase superfamily, as does the frog lens rho-crystallin. We have now determined the complete cDNA sequence of rhoB-crystallin and established that it is more closely related to the aldose reductase branch of the superfamily than to frog rho-crystallin. These gecko and frog lens proteins have thus independently been recruited from the same enzyme superfamily. Aldose reductase is implicated in the development of diabetic cataract in mammals, and, if active, rhoB-crystallin might be a potential risk for the gecko lens. Apart from a replacement 298 Cys --> Tyr, rhoB-crystallin possesses all amino acid residues thought to be required for catalytic activity of the aldose reductases. However, modeling studies of the rhoB-crystallin structure indicate that substrate specificity and nicotinamide cofactor affinity might be affected. Indeed, neither recombinant rhoB-crystallin nor the reverse mutant 298 Tyr --> Cys showed noticeable activity toward aliphatic and aromatic substrates, although cofactor binding was retained. Various other oxidoreductases are known to be recruited as abundant lens proteins in many vertebrate species; rhoB-crystallin demonstrates that an aldose reductase-related enzyme also can be modified to this end.
van Boekel
M A
MA
Department of Biochemistry, University of Nijmegen, The Netherlands. M.vanBoekel@bioch.kun.nl
van Aalten
D M
DM
Caspers
G J
GJ
Röll
B
B
de Jong
W W
WW
D000449:Aldehyde Reductase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D003459:Crystallins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D008116:Lizards / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment
D003459:Crystallins; D011994:Recombinant Proteins; C436413:rhoB crystallin protein, Lepidodactylus; D000449:Aldehyde Reductase