1pgn
From Proteopedia
(New page: 200px<br /><applet load="1pgn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pgn, resolution 2.3Å" /> '''CRYSTALLOGRAPHIC STUD...) |
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| - | [[Image:1pgn.jpg|left|200px]]<br /><applet load="1pgn" size=" | + | [[Image:1pgn.jpg|left|200px]]<br /><applet load="1pgn" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1pgn, resolution 2.3Å" /> | caption="1pgn, resolution 2.3Å" /> | ||
'''CRYSTALLOGRAPHIC STUDY OF COENZYME, COENZYME ANALOGUE AND SUBSTRATE BINDING IN 6-PHOSPHOGLUCONATE DEHYDROGENASE: IMPLICATIONS FOR NADP SPECIFICITY AND THE ENZYME MECHANISM'''<br /> | '''CRYSTALLOGRAPHIC STUDY OF COENZYME, COENZYME ANALOGUE AND SUBSTRATE BINDING IN 6-PHOSPHOGLUCONATE DEHYDROGENASE: IMPLICATIONS FOR NADP SPECIFICITY AND THE ENZYME MECHANISM'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: The nicotinamide adenine dinucleotide phosphate | + | BACKGROUND: The nicotinamide adenine dinucleotide phosphate (NADP)-dependent oxidative decarboxylase, 6-phosphogluconate dehydrogenase, is a major source of reduced coenzyme for synthesis. Enzymes later in the pentose phosphate pathway convert the reaction product, ribulose 5-phosphate, to ribose 5-phosphate. Crystallographic study of complexes with coenzyme and substrate explain the NADP dependence which determines the enzyme's metabolic role and support the proposed general base-general acid mechanism. RESULTS: The refined structures of binary coenzyme/analogue complexes show that Arg33 is ordered by binding the 2'-phosphate, and provides one face of the adenine site. The nicotinamide, while less tightly bound, is more extended when reduced than when oxidized. All substrate binding residues are conserved; the 3-hydroxyl of 6-phosphogluconate is hydrogen bonded to N zeta of Lys183 and the 3-hydrogen points towards the oxidized nicotinamide. The 6-phosphate replaces a tightly bound sulphate in the apo-enzyme. CONCLUSIONS: NADP specificity is achieved primarily by Arg33 which binds the 2'-phosphate but, in its absence, obscures the adenine pocket. The bound oxidized nicotinamide is syn; hydride transfer from bound substrate to the nicotinamide si- face is achieved with a small movement of the nicotinamide nucleotide. Lys183 may act as general base. A water bound to Gly130 in the coenzyme domain is the most likely acid required in decarboxylation. The dihydronicotinamide ring of NADPH competes for ligands with the 1-carboxyl of 6-phosphogluconate. |
==About this Structure== | ==About this Structure== | ||
| - | 1PGN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries] with SO4, NBP and POP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphogluconate_dehydrogenase_(decarboxylating) Phosphogluconate dehydrogenase (decarboxylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.44 1.1.1.44] Full crystallographic information is available from [http:// | + | 1PGN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=NBP:'>NBP</scene> and <scene name='pdbligand=POP:'>POP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphogluconate_dehydrogenase_(decarboxylating) Phosphogluconate dehydrogenase (decarboxylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.44 1.1.1.44] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PGN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Phosphogluconate dehydrogenase (decarboxylating)]] | [[Category: Phosphogluconate dehydrogenase (decarboxylating)]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Adams, M | + | [[Category: Adams, M J.]] |
[[Category: Gover, S.]] | [[Category: Gover, S.]] | ||
[[Category: Phillips, C.]] | [[Category: Phillips, C.]] | ||
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[[Category: oxidoreductase (choh(d)-nadp+(a))]] | [[Category: oxidoreductase (choh(d)-nadp+(a))]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:28:36 2008'' |
Revision as of 12:28, 21 February 2008
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CRYSTALLOGRAPHIC STUDY OF COENZYME, COENZYME ANALOGUE AND SUBSTRATE BINDING IN 6-PHOSPHOGLUCONATE DEHYDROGENASE: IMPLICATIONS FOR NADP SPECIFICITY AND THE ENZYME MECHANISM
Overview
BACKGROUND: The nicotinamide adenine dinucleotide phosphate (NADP)-dependent oxidative decarboxylase, 6-phosphogluconate dehydrogenase, is a major source of reduced coenzyme for synthesis. Enzymes later in the pentose phosphate pathway convert the reaction product, ribulose 5-phosphate, to ribose 5-phosphate. Crystallographic study of complexes with coenzyme and substrate explain the NADP dependence which determines the enzyme's metabolic role and support the proposed general base-general acid mechanism. RESULTS: The refined structures of binary coenzyme/analogue complexes show that Arg33 is ordered by binding the 2'-phosphate, and provides one face of the adenine site. The nicotinamide, while less tightly bound, is more extended when reduced than when oxidized. All substrate binding residues are conserved; the 3-hydroxyl of 6-phosphogluconate is hydrogen bonded to N zeta of Lys183 and the 3-hydrogen points towards the oxidized nicotinamide. The 6-phosphate replaces a tightly bound sulphate in the apo-enzyme. CONCLUSIONS: NADP specificity is achieved primarily by Arg33 which binds the 2'-phosphate but, in its absence, obscures the adenine pocket. The bound oxidized nicotinamide is syn; hydride transfer from bound substrate to the nicotinamide si- face is achieved with a small movement of the nicotinamide nucleotide. Lys183 may act as general base. A water bound to Gly130 in the coenzyme domain is the most likely acid required in decarboxylation. The dihydronicotinamide ring of NADPH competes for ligands with the 1-carboxyl of 6-phosphogluconate.
About this Structure
1PGN is a Single protein structure of sequence from Ovis aries with , and as ligands. Active as Phosphogluconate dehydrogenase (decarboxylating), with EC number 1.1.1.44 Full crystallographic information is available from OCA.
Reference
Crystallographic study of coenzyme, coenzyme analogue and substrate binding in 6-phosphogluconate dehydrogenase: implications for NADP specificity and the enzyme mechanism., Adams MJ, Ellis GH, Gover S, Naylor CE, Phillips C, Structure. 1994 Jul 15;2(7):651-68. PMID:7922042
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