Article info 2014 2 (4)    002  (04)   pp.  129 ~ 134
Title Selection of differential chirality of (R)- and (S)-3-hydroxybutyryl-CoA dehydrogenases
Authors Jieun Kim and Kyung-Jin Kim
Institutions Structural and Molecular Biology Laboratory, School of Life Sciences, Kyungpook National University, Daegu 702-701, Korea. *Correspondence: kkim@knu.ac.kr
Abstract (R)- and (S)-3-hydroxybutyryl-CoA dehydrogenases from Ralstonia eutropha H16 play a significant role in the biosynthesis of bioplastics and biofuels. (R)-3-hydroxybutyryl-CoA dehydrogenase (RePhaB) is an enzyme that is involved in the synthetic pathway of polyalkanoates (PHA) which are used to make bioplastics, implant biomaterials, and biofuel. Whereas, (S)-3-hydroxybutyryl-CoA dehydrogenase (RePaaH1) is an enzyme that is involved in the biosynthesis of the n-butanol. Although both these enzymes utilize Acetoacetyl-CoA as a substrate to produce 3-hydroxybutyryl-CoA, the chirality of the final product is different—(R)-3-hydroxybutyryl-CoA by RePhaB and (S)-3-hydroxybutyryl-CoA by RePaaH1. Crystal structures of RePhaB and RePaaH1 show remarkable differences in their structures, oligomeric states, and cofactor specificity. RePhaB forms a tetramer, whereas RePaaH1 forms a dimer. Their cofactor requirements are also different— NADPH and NADH for RePhaB and RePaaH1, respectively. Moreover, their substrate binding modes are also substantially different. Interestingly, both enzymes undergo a conformational change upon binding to acetoaceryl-CoA substrate. In RePhaB, the lid-domain undergoes a large conformational change of about 4.6 Å to form a substrate pocket, whereas only a small structural change is observed in RePaaH1. Comparison of active sites of these enzymes reveals the differences in the position of catalytic residues, which ultimately determines the differential chirality of their products.