PDBsum entry 1pgp

Oxidoreductase (choh(d)-NADP+(a))

PDB id: 1pgp

Contents

Protein chain

473 a.a. *

Ligands

6PG

SO4

Waters ×398

* Residue conservation analysis

PDB id:

1pgp

Name:

Oxidoreductase (choh(d)-NADP+(a))

Title:

Crystallographic study of coenzyme, coenzyme analogue and substrate binding in 6-phosphogluconate dehydrogenase: implications for NADP specificity and the enzyme mechanism

Structure:

6-phosphogluconate dehydrogenase. Chain: a. Engineered: yes

Source:

Ovis aries. Sheep. Organism_taxid: 9940

Biol. unit:

Dimer (from PQS)

Resolution:

2.50Å R-factor: 0.170

Authors:

M.J.Adams,C.Phillips,S.Gover,C.E.Naylor

Key ref:

M.J.Adams et al. (1994). Crystallographic study of coenzyme, coenzyme analogue and substrate binding in 6-phosphogluconate dehydrogenase: implications for NADP specificity and the enzyme mechanism. Structure, 2, 651-668. PubMed id: 7922042 DOI: 10.1016/S0969-2126(00)00066-6

Date:

18-Jul-94 Release date: 27-Feb-95

Protein chain

P00349  (6PGD_SHEEP) -  6-phosphogluconate dehydrogenase, decarboxylating from Ovis aries

Seq: 483 a.a.

Struc: 473 a.a.

Enzyme reactions

• Enzyme class: E.C.1.1.1.44 - phosphogluconate dehydrogenase (NADP(+)-dependent, decarboxylating).
• Pathway: Pentose Phosphate Pathway (early stages)
• Reaction: 6-phospho-D-gluconate + NADP⁺ = D-ribulose 5-phosphate + CO2 + NADPH

6-phospho-D-gluconate (Bound ligand (Het Group name = 6PG) corresponds exactly) + NADP(+) = D-ribulose 5-phosphate + CO2 + NADPH

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/S0969-2126(00)00066-6

Structure 2:651-668 (1994)

PubMed id: 7922042

Crystallographic study of coenzyme, coenzyme analogue and substrate binding in 6-phosphogluconate dehydrogenase: implications for NADP specificity and the enzyme mechanism.

M.J.Adams, G.H.Ellis, S.Gover, C.E.Naylor, C.Phillips.

ABSTRACT

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.

Selected figure(s)

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.

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]).

The above figures are reprinted by permission from Cell Press: Structure (1994, 2, 651-668) copyright 1994.

Figures were selected by an automated process.