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 hexagonal, 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 structure solution has been successfully obtained by using the refined structure of the apoenzyme as the search model. The crystallographic R factor is currently equal to 0.24 after energy minimization using data between 8 and 3.0 Angstrom resolution. The aldehyde reductase-NADPH complex model is supported by electron density corresponding to NADPH not included in the search model. The tertiary structure of aldehyde reductase consists of a beta/alpha-barrel with the coenzyme-binding site located at the carboxy-terminal end of the strands of the barrel. The structure of aldehyde reductase-NADPH binary complex will help clarify the mechanism of action for this enzyme and will lead to the development of pharmacologic agents to delay or prevent diabetic complications.