PDBsum entry 3mpi

Oxidoreductase

PDB id: 3mpi

Contents

Protein chains

391 a.a. *

Ligands

FAD ×4

GRA ×4

Waters ×476

* Residue conservation analysis

PDB id:

3mpi

Name:

Oxidoreductase

Title:

Structure of the glutaryl-coenzyme a dehydrogenase glutaryl-coa complex

Structure:

Glutaryl-coa dehydrogenase. Chain: a, b, c, d. Engineered: yes

Source:

Desulfococcus multivorans. Organism_taxid: 897. Gene: acd, gi228015642. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.05Å R-factor: 0.178 R-free: 0.219

Authors:

S.Wischgoll,E.Warkentin,M.Boll,U.Ermler

Key ref:

S.Wischgoll et al. (2010). Structural basis for promoting and preventing decarboxylation in glutaryl-coenzyme a dehydrogenases. Biochemistry, 49, 5350-5357. PubMed id: 20486657

Date:

27-Apr-10 Release date: 18-Aug-10

Protein chains

C3UVB0  (ACD_DESML) -  Glutaryl-CoA dehydrogenase from Desulfococcus multivorans

Seq: 389 a.a.

Struc: 391 a.a.

Enzyme reactions

• Enzyme class: E.C.1.3.99.32 - glutaryl-CoA dehydrogenase (acceptor).
• Reaction: glutaryl-CoA + A = (2E)-glutaconyl-CoA + AH2

glutaryl-CoA + (Bound ligand (Het Group name = GRA) corresponds exactly) = (2E)-glutaconyl-CoA + AH2

• Cofactor: FAD

FAD (Bound ligand (Het Group name = FAD) corresponds exactly)

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

Added reference

Biochemistry 49:5350-5357 (2010)

PubMed id: 20486657

Structural basis for promoting and preventing decarboxylation in glutaryl-coenzyme a dehydrogenases.

S.Wischgoll, U.Demmer, E.Warkentin, R.Günther, M.Boll, U.Ermler.

ABSTRACT

Glutaryl-coenzyme A dehydrogenases (GDHs) involved in amino acid degradation were thought to catalyze both the dehydrogenation and decarboxylation of glutaryl-coenzyme A to crotonyl-coenzyme A and CO(2). Recently, a structurally related but nondecarboxylating, glutaconyl-coenzyme A-forming GDH was characterized in the obligately anaerobic bacteria Desulfococcus multivorans (GDH(Des)) which conserves the free energy of decarboxylation by a Na(+)-pumping glutaconyl-coenzyme A decarboxylase. To understand the distinct catalytic behavior of the two GDH types on an atomic basis, we determined the crystal structure of GDH(Des) with and without glutaconyl-coenzyme A bound at 2.05 and 2.1 A resolution, respectively. The decarboxylating and nondecarboxylating capabilities are provided by complex structural changes around the glutaconyl carboxylate group, the key factor being a Tyr --> Val exchange strictly conserved between the two GDH types. As a result, the interaction between the glutaconyl carboxylate and the guanidinium group of a conserved arginine is stronger in GDH(Des) (short and planar bidentate hydrogen bond) than in the decarboxylating human GDH (longer and monodentate hydrogen bond), which is corroborated by molecular dynamics studies. The identified structural changes prevent decarboxylation (i) by strengthening the C4-C5 bond of glutaconyl-coenzyme A, (ii) by reducing the leaving group potential of CO(2), and (iii) by increasing the distance between the C4 atom (negatively charged in the dienolate transition state) and the adjacent glutamic acid.