3mpi

Structure of the glutaryl-coenzyme A dehydrogenase glutaryl-CoA complex

spinqualitylabelsall models 3mpi, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3mpi is a 4 chain structure with sequence from Desulfococcus multivorans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.05Å Ligands: FAD, GRA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ACD_DESML Catalyzes the dehydrogenation of Glutaryl-CoA to glutaconyl-CoA. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Structural basis for promoting and preventing decarboxylation in glutaryl-coenzyme a dehydrogenases.,Wischgoll S, Demmer U, Warkentin E, Gunther R, Boll M, Ermler U Biochemistry. 2010 Jun 29;49(25):5350-7. PMID:20486657 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acyl-CoA dehydrogenase 3D structures Glutaryl-CoA dehydrogenase

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