2II4

Crystal structure of a cubic core of the dihydrolipoamide acyltransferase (E2b) component in the branched-chain alpha-ketoacid dehydrogenase complex (BCKDC), Coenzyme A-bound form

Summary for 2II4

• Entry DOI: 10.2210/pdb2ii4/pdb
• Related: 2IHW 2II3 2II5
• Descriptor: Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, CHLORIDE ION, COENZYME A, ... (4 entities in total)
• Functional Keywords: cubic core, homo trimer, coa-bound form, transferase
• Biological source: Bos taurus (cattle)
• Cellular location: Mitochondrion matrix : P11181
• Total number of polymer chains: 8
• Total formula weight: 236378.32

Authors

Kato, M.,Wynn, R.M.,Chuang, J.L.,Brautigam, C.A.,Custorio, M.,Chuang, D.T. (deposition date: 2006-09-27, release date: 2006-12-26, Last modification date: 2024-02-21)

Primary citation

Kato, M.,Wynn, R.M.,Chuang, J.L.,Brautigam, C.A.,Custorio, M.,Chuang, D.T.
A synchronized substrate-gating mechanism revealed by cubic-core structure of the bovine branched-chain alpha-ketoacid dehydrogenase complex.
Embo J., 25:5983-5994, 2006

PubMed Abstract: The dihydrolipoamide acyltransferase (E2b) component of the branched-chain alpha-ketoacid dehydrogenase complex forms a cubic scaffold that catalyzes acyltransfer from S-acyldihydrolipoamide to CoA to produce acyl-CoA. We have determined the first crystal structures of a mammalian (bovine) E2b core domain with and without a bound CoA or acyl-CoA. These structures reveal both hydrophobic and the previously unreported ionic interactions between two-fold-related trimers that build up the cubic core. The entrance of the dihydrolipoamide-binding site in a 30-A long active-site channel is closed in the apo and acyl-CoA-bound structures. CoA binding to one entrance of the channel promotes a conformational change in the channel, resulting in the opening of the opposite dihydrolipoamide gate. Binding experiments show that the affinity of the E2b core for dihydrolipoamide is markedly increased in the presence of CoA. The result buttresses the model that CoA binding is responsible for the opening of the dihydrolipoamide gate. We suggest that this gating mechanism synchronizes the binding of the two substrates to the active-site channel, which serves as a feed-forward switch to coordinate the E2b-catalyzed acyltransfer reaction.

PubMed: 17124494
DOI: 10.1038/sj.emboj.7601444

Experimental method

X-RAY DIFFRACTION (2.59 Å)