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PDBsum entry 1pgo
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Oxidoreductase (choh(d)-NADP+(a))
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PDB id
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1pgo
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References listed in PDB file
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Key reference
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Title
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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.
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Authors
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M.J.Adams,
G.H.Ellis,
S.Gover,
C.E.Naylor,
C.Phillips.
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Ref.
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Structure, 1994,
2,
651-668.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 8.
Figure 8. Stereo pair showing Arg33 in its conformation in the
apo-enzyme (blue) and in binary complexes (red), and
demonstrating its role in forming the adenine pocket. Figure
8. Stereo pair showing Arg33 in its conformation in the
apo-enzyme (blue) and in binary complexes (red), and
demonstrating its role in forming the adenine pocket.
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Figure 14.
Figure 14. Steps of the general base–acid mechanism for 6PG
oxidative decarboxylation by 6PGDH (after Berdis and Cook [21]).
Figure 14. Steps of the general base–acid mechanism for 6PG
oxidative decarboxylation by 6PGDH (after Berdis and Cook
[[3]21]).
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The above figures are
reprinted
by permission from Cell Press:
Structure
(1994,
2,
651-668)
copyright 1994.
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Secondary reference #1
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Title
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Structure of 6-Phosphogluconate dehydrogenase refined at 2 a resolution.
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Authors
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C.Phillips,
S.Gover,
M.J.Adams.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 1995,
51,
290-304.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
86%.
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Figure 7.
Fig. 7. The topology diagram.
Secondary-structural elements,
as defined by the
DSSP
program
(Kabsch & Sander, 1983), and
domains are labelled. The copies
of the duplicated five-helix
motif are shaded blue and red,
respectively.
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Figure 9.
Fig. 9. Distortions in the regular
secondary elements ~G and
ag due to the incorporation of
Pro 142 and Pro 150, respectively.
The DSSP
assignment begins
c~g at Trp149, whereas the
hydrogen-bonding network starts
at residue 142.
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The above figures are
reproduced from the cited reference
with permission from the IUCr
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Secondary reference #2
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Title
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The structure of 6-Phosphogluconate dehydrogenase refined at 2.5 a resolution.
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Authors
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M.J.Adams,
S.Gover,
R.Leaback,
C.Phillips,
D.O.Somers.
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Ref.
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Acta Crystallogr B, 1991,
47,
817-820.
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PubMed id
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