PDBsum entry: 1hwx

Oxidoreductase

PDB id: 1hwx

Contents

Protein chains

(+ 0 more) 501 a.a. *

Ligands

GLU ×6

GTP ×6

NAI ×12

Waters ×294

* Residue conservation analysis

Superseded by:

3mw9

PDB id:

1hwx

Name:

Oxidoreductase

Title:

Crystal structure of bovine liver glutamate dehydrogenase co with gtp, nadh, and l-glutamic acid

Structure:

Glutamate dehydrogenase. Chain: a, b, c, d, e, f. Synonym: gdh. Ec: 1.4.1.3

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Organ: liver. Organelle: mitochondria. Cellular_location: inner mitochondrial matrix

Biol. unit:

Hexamer (from PQS)

Resolution:

2.50Å R-factor: 0.170 R-free: 0.230

Authors:

P.E.Peterson,T.J.Smith

Key ref:

P.E.Peterson and T.J.Smith (1999). The structure of bovine glutamate dehydrogenase provides insights into the mechanism of allostery. Structure, 7, 769-782. PubMed id: 10425679 DOI: 10.1016/S0969-2126(99)80101-4

Date:

10-Jan-01 Release date: 31-Jan-01

Protein chains

P00366  (DHE3_BOVIN) -  Glutamate dehydrogenase 1, mitochondrial

Seq: 558 a.a.

Struc: 501 a.a.*

* PDB and UniProt seqs differ at 17 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.1.4.1.3 - Glutamate dehydrogenase (NAD(P)(+)).
• Reaction: L-glutamate + H₂O + NAD(P)(+) = 2-oxoglutarate + NH₃ + NAD(P)H

L-glutamate (Bound ligand (Het Group name = GLU) corresponds exactly) + H(2)O + NAD(P)(+) (Bound ligand (Het Group name = NAI) matches with 91.00% similarity) = 2-oxoglutarate + NH(3) + NAD(P)H

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

reference

DOI no: 10.1016/S0969-2126(99)80101-4

Structure 7:769-782 (1999)

PubMed id: 10425679

The structure of bovine glutamate dehydrogenase provides insights into the mechanism of allostery.

P.E.Peterson, T.J.Smith.

ABSTRACT

BACKGROUND: Bovine glutamate dehydrogenase (boGDH) is a homohexameric, mitochondrial enzyme that reversibly catalyzes the oxidative deamination of L-glutamate to 2-oxoglutarate using either NADP(H) or NAD(H) with comparable efficacy. GDH represents a key enzymatic link between catabolic and biosynthetic pathways, and is therefore ubiquitous in both higher and lower organisms. Only mammalian GDH exhibits strong negative cooperativity with respect to the coenzyme, however, and is regulated by a large number of allosteric effectors. RESULTS: The atomic structure of boGDH in complex with NADH, glutamate, and the allosteric inhibitor GTP has been determined to 2.8 A resolution. The major difference between the bacterial and bovine GDH structures is the presence of an additional 'antenna' in boGDH that protrudes from each trimer, twisting counterclockwise along the threefold axis. NADH and glutamate are clearly observed in the active site, but the contacts differ slightly from those observed in Clostridium symbiosum GDH. A second, inhibitory NADH molecule lies buried in the core of the hexamer. Finally, two GTP molecules bind near the hinge region connecting the NAD(+)- and glutamate-binding domains. CONCLUSIONS: We propose that the antenna serves as an intersubunit communication conduit during negative cooperativity and allosteric regulation. GTP and NADH inhibit GDH by keeping the catalytic cleft in a closed conformation. In contrast, ADP probably binds to the back of the NAD(+)-binding domain and activates the enzyme by keeping the catalytic cleft open. Extensive contacts between antennae within the crystal lattice may represent hexamer interactions in solution and, perhaps, with other enzymes within the mitochondrial matrix.

Selected figure(s)

Figure 8.
Figure 8. Location of the genetic defects found in human GDH that lead to hyperammonemia and hyperinsulinism. The view and color scheme are the same as inFigure 2. The GTP #1 molecule is represented by a ball-and-stick model; the sidechains of residues observed to mutate in human GDH are shown in stick form. (The figure was created using MolView [31].)

The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 769-782) copyright 1999.

Figure was selected by an automated process.