Download MendeleyNadp+ and Nad+ Binding to the Dual Coenzyme Specific Enzyme Leuconostoc Mesenteroides Glucose 6-Phosphate Dehydrogenase: Different Interdomain Hinge Angles are Seen in Different Binary and Ternary Complexes
Naylor, C.E., Gover, S., Basak, A.K., Cosgrove, M.S., Levy, H.R., Adams, M.J.(2001) Acta Crystallogr D Biol Crystallogr 57: 635
- PubMed: 11320304
- DOI: https://doi.org/10.1107/s0907444901003420
- Primary Citation of Related Structures:
1H93, 1H94, 1H9A, 1H9B - PubMed Abstract:
The reduced coenzymes NADH and NADPH only differ by one phosphate, but in the cell NADH provides reducing power for catabolism while NADPH is utilized in biosynthetic pathways. Enzymes almost invariably discriminate between the coenzymes, but glucose 6-phosphate dehydrogenase (G6PD) from Leuconostoc mesenteroides is rare in being functionally dual specific. In order to elucidate the coenzyme selectivity, the structures of NADP(+)- and NAD(+)-complexed L. mesenteroides G6PD have been determined including data to 2.2 and 2.5 A resolution, respectively, and compared with unliganded G6PD crystallized in the same space groups. Coenzyme binding is also compared with that in a ternary complex of a mutant in which Asp177 in the active site has been mutated to asparagine. There are no gross structural differences between the complexes. In both binary complexes, the enzyme interdomain hinge angle has opened. NADP(+) binds to the furthest open form; of the residues within the coenzyme domain, only Arg46 moves, interacting with the 2'-phosphate and adenine. NAD(+) is less well defined in the binding site; smaller hinge opening is seen but larger local changes: Arg46 is displaced, Thr14 bonds the 3'-hydroxyl and Gln47 bonds the 2'-hydroxyl. In the ternary complex, the hinge angle has closed; only the adenine nucleotide is ordered in the binding site. Arg46 again provides most binding interactions.
Organizational Affiliation:
Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Rex Richards Building, South Parks Road, Oxford OX1 3QU, England, UK.
