Structural and molecular biology of type I galactosemia: Disease-associated mutations

摘要: Type I galactosemia results from reduced galactose 1-phosphate uridylyltransferase (GALT) activity. Signs of disease include damage to the eyes, brain, liver, and ovaries. However, exact nature severity pathology depends on mutation(s) in patient's genes his/her environment. Considerable enzymological structural knowledge has been accumulated this provides a basis explain, at biochemical level, impairment enzyme more than 230 disease-associated variants, which have described. The most common variant, Q188R, occurs close active site dimer interface. substitution probably disrupts both UDP-sugar binding homodimer stability. Other alterations, for example K285N, occur surface likely affect folding stability enzyme. There are number unanswered questions field, require resolution. These possibility that main enzymes metabolism form supramolecular complex need high resolution crystal structure human GALT. © 2011 IUBMB Life, 63(11): 949–954,