8P5R

Crystal structure of full-length, homohexameric 2-oxoglutarate dehydrogenase KGD from Mycobacterium smegmatis in complex with GarA

Summary for 8P5R

• Entry DOI: 10.2210/pdb8p5r/pdb
• Descriptor: Multifunctional 2-oxoglutarate metabolism enzyme, Glycogen accumulation regulator GarA, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: 2-oxoglutarate dehydrogenase; odh; kgd; oxidoreductase, oxidoreductase
• Biological source: Mycolicibacterium smegmatis MC2 155; More
• Total number of polymer chains: 16
• Total formula weight: 1488093.36

Authors

Wagner, T.,Mechaly, A.M.,Alzari, P.M.,Bellinzoni, M. (deposition date: 2023-05-24, release date: 2023-08-16, Last modification date: 2023-08-23)

Primary citation

Yang, L.,Wagner, T.,Mechaly, A.,Boyko, A.,Bruch, E.M.,Megrian, D.,Gubellini, F.,Alzari, P.M.,Bellinzoni, M.
High resolution cryo-EM and crystallographic snapshots of the actinobacterial two-in-one 2-oxoglutarate dehydrogenase.
Nat Commun, 14:4851-4851, 2023

PubMed Abstract: Actinobacteria possess unique ways to regulate the oxoglutarate metabolic node. Contrary to most organisms in which three enzymes compose the 2-oxoglutarate dehydrogenase complex (ODH), actinobacteria rely on a two-in-one protein (OdhA) in which both the oxidative decarboxylation and succinyl transferase steps are carried out by the same polypeptide. Here we describe high-resolution cryo-EM and crystallographic snapshots of representative enzymes from Mycobacterium smegmatis and Corynebacterium glutamicum, showing that OdhA is an 800-kDa homohexamer that assembles into a three-blade propeller shape. The obligate trimeric and dimeric states of the acyltransferase and dehydrogenase domains, respectively, are critical for maintaining the overall assembly, where both domains interact via subtle readjustments of their interfaces. Complexes obtained with substrate analogues, reaction products and allosteric regulators illustrate how these domains operate. Furthermore, we provide additional insights into the phosphorylation-dependent regulation of this enzymatic machinery by the signalling protein OdhI.

PubMed: 37563123
DOI: 10.1038/s41467-023-40253-6

Experimental method

X-RAY DIFFRACTION (4.562 Å)