PDBsum entry 3jd0

Oxidoreductase

PDB id: 3jd0

Contents

Protein chains

(+ 0 more) 496 a.a.

Ligands

GTP ×6

PDB id:

3jd0

Name:

Oxidoreductase

Title:

Glutamate dehydrogenase in complex with gtp

Structure:

Glutamate dehydrogenase 1, mitochondrial. Chain: a, b, c, d, e, f. Fragment: unp residues 58-558. Synonym: gdh 1. Ec: 1.4.1.3

Source:

Bos taurus. Bovine. Organism_taxid: 9913

Authors:

M.J.Borgnia,S.Banerjee,A.Merk,D.Matthies,A.Bartesaghi,P.Rao, J.Pierson,L.A.Earl,V.Falconieri,S.Subramaniam,J.L.S.Milne

Key ref:

M.J.Borgnia et al. (2016). Using Cryo-EM to Map Small Ligands on Dynamic Metabolic Enzymes: Studies with Glutamate Dehydrogenase. Mol Pharmacol, 89, 645-651. PubMed id: 27036132 DOI: 10.1124/mol.116.103382

Date:

28-Mar-16 Release date: 27-Apr-16

Protein chains

P00366  (DHE3_BOVIN) -  Glutamate dehydrogenase 1, mitochondrial from Bos taurus

Seq: 558 a.a.

Struc: 496 a.a.

Enzyme reactions

• Enzyme class: E.C.1.4.1.3 - glutamate dehydrogenase [NAD(P)(+)].
• Reaction:
  1. L-glutamate + NAD⁺ + H2O = 2-oxoglutarate + NH4⁺ + NADH + H⁺
  2. L-glutamate + NADP⁺ + H2O = 2-oxoglutarate + NH4⁺ + NADPH + H⁺

L-glutamate + NAD(+) (Bound ligand (Het Group name = GTP) matches with 55.10% similarity) + H2O = 2-oxoglutarate + NH4(+) + NADH + H(+)

L-glutamate + NADP(+) (Bound ligand (Het Group name = GTP) matches with 50.94% similarity) + H2O = 2-oxoglutarate + NH4(+) + NADPH + H(+)

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

reference

DOI no: 10.1124/mol.116.103382

Mol Pharmacol 89:645-651 (2016)

PubMed id: 27036132

Using Cryo-EM to Map Small Ligands on Dynamic Metabolic Enzymes: Studies with Glutamate Dehydrogenase.

M.J.Borgnia, S.Banerjee, A.Merk, D.Matthies, A.Bartesaghi, P.Rao, J.Pierson, L.A.Earl, V.Falconieri, S.Subramaniam, J.L.Milne.

ABSTRACT

Cryo-electron microscopy (cryo-EM) methods are now being used to determine structures at near-atomic resolution and have great promise in molecular pharmacology, especially in the context of mapping the binding of small-molecule ligands to protein complexes that display conformational flexibility. We illustrate this here using glutamate dehydrogenase (GDH), a 336-kDa metabolic enzyme that catalyzes the oxidative deamination of glutamate. Dysregulation of GDH leads to a variety of metabolic and neurologic disorders. Here, we report near-atomic resolution cryo-EM structures, at resolutions ranging from 3.2 Å to 3.6 Å for GDH complexes, including complexes for which crystal structures are not available. We show that the binding of the coenzyme NADH alone or in concert with GTP results in a binary mixture in which the enzyme is in either an "open" or "closed" state. Whereas the structure of NADH in the active site is similar between the open and closed states, it is unexpectedly different at the regulatory site. Our studies thus demonstrate that even in instances when there is considerable structural information available from X-ray crystallography, cryo-EM methods can provide useful complementary insights into regulatory mechanisms for dynamic protein complexes.