CRYSTALLIZATION AND PRELIMINARY STRUCTURE OF PORCINE ALDEHYDE REDUCTASE NADPH BINARY COMPLEX

Porcine aldehyde reductase-NADPH binary complex has been crystallized from a buffered ammonium sulfate solution. The crystal form is hexagon al, space group P6(5)22, with a = b = 67.2, c = 243.7 Angstrom, alpha = beta = 90.0 and gamma = 120.0 degrees. A molecular-replacement struc ture solution has been successfully obtained by using the refined stru cture of the apoenzyme as the search model. The crystallographic R fac tor is currently equal to 0.24 after energy minimization using data be tween 8 and 3.0 Angstrom resolution. The aldehyde reductase-NADPH comp lex model is supported by electron density corresponding to NADPH not included in the search model. The tertiary structure of aldehyde reduc tase consists of a beta/alpha-barrel with the coenzyme-binding site lo cated at the carboxy-terminal end of the strands of the barrel. The st ructure of aldehyde reductase-NADPH binary complex will help clarify t he mechanism of action for this enzyme and will lead to the developmen t of pharmacologic agents to delay or prevent diabetic complications.