Evolution of the aldose reductase-related gecko eye lens protein rho B-crystallin: A sheep in wolf's clothing

rhoB-crystallin (AJ245805) is a major protein component (20%) in the eye le ns 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 p-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 p-crystalli n. These gecko and frog lens proteins have thus independently been recruite d from the same enzyme superfamily. Aldose reductase is implicated in the d evelopment 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, model ing studies of the rhoB-crystallin structure indicate that substrate specif icity and nicotinamide cofactor affinity might be affected. Indeed, neither recombinant rhoB-clystallin nor the reverse mutant 298 Tyr --> Cys showed noticeable activity toward aliphatic and aromatic substrates, although cofa ctor binding was retained. Various other oxidoreductases are known to be re cruited as abundant. lens proteins in many vertebrate species; rhoB-crystal lin demonstrates that an aldose reductase-related enzyme also can be modifi ed to this end.