NADP+ 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

Acta Crystallographica. Section D, Biological Crystallography
C NaylorMargaret J Adams

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....Continue Reading

Citations

Jun 18, 2011·Bioconjugate Chemistry·May L ChiuHarold G Monbouquette
Jul 14, 2016·Indian Journal of Hematology & Blood Transfusion : an Official Journal of Indian Society of Hematology and Blood Transfusion·Xiaowen ChenFurong Liu
Jun 7, 2006·Proteins·Vincent ChaptalSolange Moréra
Sep 21, 2016·ACS Synthetic Biology·Jackson K B CahnFrances H Arnold
Oct 28, 2019·Biotechnology and Applied Biochemistry·Mei-Na YangDong-Hao Zhang
Feb 4, 2019·Applied Microbiology and Biotechnology·Emrah ÖzcanTunahan Çakır
Apr 8, 2015·The Biochemical Journal·Jackson K B CahnFrances H Arnold

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