PDBsum entry: 1sc6

Oxidoreductase

PDB id: 1sc6

Contents

Protein chains

390 a.a. *

Ligands

NAD ×4

Waters ×463

* Residue conservation analysis

PDB id:

1sc6

Name:

Oxidoreductase

Title:

Crystal structure of w139g d-3-phosphoglycerate dehydrogenase complexed with NAD+

Structure:

D-3-phosphoglycerate dehydrogenase. Chain: a, b, c, d. Synonym: pgdh. Engineered: yes. Mutation: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: sera, b2913, c3494, z4251, ecs3784, sf2898, s3098. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.09Å R-factor: 0.220 R-free: 0.260

Authors:

J.K.Bell,G.A.Grant,L.J.Banaszak

Key ref:

J.K.Bell et al. (2004). Multiconformational states in phosphoglycerate dehydrogenase. Biochemistry, 43, 3450-3458. PubMed id: 15035616 DOI: 10.1021/bi035462e

Date:

11-Feb-04 Release date: 22-Feb-05

Protein chains

P0A9T0  (SERA_ECOLI) -  D-3-phosphoglycerate dehydrogenase

Seq: 410 a.a.

Struc: 390 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.1.1.1.95 - Phosphoglycerate dehydrogenase.
• Reaction:
  1. 3-phospho-D-glycerate + NAD⁺ = 3-phosphonooxypyruvate + NADH
  2. 2-hydroxyglutarate + NAD⁺ = 2-oxoglutarate + NADH

3-phospho-D-glycerate + NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly) = 3-phosphonooxypyruvate + NADH

2-hydroxyglutarate + NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly) = 2-oxoglutarate + NADH

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

 Gene Ontology (GO) functional annotation 

• Biological process: metabolic process (4 terms)
• Biochemical function: nucleotide binding (8 terms)

reference

DOI no: 10.1021/bi035462e

Biochemistry 43:3450-3458 (2004)

PubMed id: 15035616

Multiconformational states in phosphoglycerate dehydrogenase.

J.K.Bell, G.A.Grant, L.J.Banaszak.

ABSTRACT

Phosphoglycerate dehydrogenase (PGDH) catalyzes the first step in the serine biosynthetic pathway. In lower plants and bacteria, the PGDH reaction is regulated by the end-product of the pathway, serine. The regulation occurs through a V(max) mechanism with serine binding and inhibition occurring in a cooperative manner. The three-dimensional structure of the serine inhibited enzyme, determined by previous work, showed a tetrameric enzyme with 222 symmetry and an unusual overall toroidal appearance. To characterize the allosteric, cooperative effects of serine, we identified W139G PGDH as an enzymatically active mutant responsive to serine but not in a cooperative manner. The position of W139 near a subunit interface and the active site cleft suggested that this residue is a key player in relaying allosteric effects. The 2.09 A crystal structure of W139G-PGDH, determined in the absence of serine, revealed major quaternary and tertiary structural changes. Contrary to the wildtype enzyme where residues encompassing residue 139 formed extensive intersubunit contacts, the corresponding residues in the mutant were conformationally flexible. Within each of the three-domain subunits, one domain has rotated approximately 42 degrees relative to the other two. The resulting quaternary structure is now in a novel conformation creating new subunit-to-subunit contacts and illustrates the unusual flexibility in this V(max) regulated enzyme. Although changes at the regulatory domain interface have implications in other enzymes containing a similar regulatory or ACT domain, the serine binding site in W139G PGDH is essentially unchanged from the wildtype enzyme. The structural and previous biochemical characterization of W139G PGDH suggests that the allosteric regulation of PGDH is mediated not only by changes occurring at the ACT domain interface but also by conformational changes at the interface encompassing residue W139.