1h9a: Difference between revisions

Revision as of 13:59, 21 February 2008

COMPLEX OF ACTIVE MUTANT (Q365->C) OF GLUCOSE 6-PHOSPHATE DEHYDROGENASE FROM L. MESENTEROIDES WITH COENZYME NADP

OverviewOverview

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.

About this StructureAbout this Structure

1H9A is a Single protein structure of sequence from Leuconostoc mesenteroides with and as ligands. Active as Glucose-6-phosphate 1-dehydrogenase, with EC number 1.1.1.49 Known structural/functional Sites: and . Full crystallographic information is available from OCA.

ReferenceReference

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., Naylor CE, Gover S, Basak AK, Cosgrove MS, Levy HR, Adams MJ, Acta Crystallogr D Biol Crystallogr. 2001 May;57(Pt 5):635-48. Epub 2001, Apr 24. PMID:11320304

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 ==Overview==
-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.
+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.
 ==About this Structure==
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 [[Category: Leuconostoc mesenteroides]]
 [[Category: Single protein]]
-[[Category: Adams, M.J.]]
+[[Category: Adams, M J.]]
 [[Category: Gover, S.]]
-[[Category: Naylor, C.E.]]
+[[Category: Naylor, C E.]]
 [[Category: NAP]]
 [[Category: SO4]]
@@ Line 22: / Line 22: @@
 [[Category: oxidoreductase (choh(d) - nad(p))]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 09:47:54 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:58:54 2008''