1ON9

Transcarboxylase 12S crystal structure: hexamer assembly and substrate binding to a multienzyme core (with hydrolyzed methylmalonyl-coenzyme a bound)

1ON9 の概要

• エントリーDOI: 10.2210/pdb1on9/pdb
• 関連するPDBエントリー: 1ON3
• 分子名称: Methylmalonyl-CoA carboxyltransferase 12S subunit, CADMIUM ION, METHYLMALONYL-COENZYME A, ... (5 entities in total)
• 機能のキーワード: carboxyl transferase, domain duplication, multienzyme complex, transcarboxylase, transferase
• 由来する生物種: Propionibacterium freudenreichii
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 343625.89

構造登録者

Hall, P.R.,Wang, Y.-F.,Rivera-Hainaj, R.E.,Zheng, X.,Pustai-Carey, M.,Carey, P.R.,Yee, V.C. (登録日: 2003-02-27, 公開日: 2003-05-20, 最終更新日: 2024-02-14)

主引用文献

Hall, P.R.,Wang, Y.-F.,Rivera-Hainaj, R.E.,Zheng, X.,Pustai-Carey, M.,Carey, P.R.,Yee, V.C.
Transcarboxylase 12S crystal structure: hexamer assembly and substrate binding to a multienzyme core
Embo J., 22:2334-2347, 2003

PubMed Abstract: Transcarboxylase from Propionibacterium shermanii is a 1.2 MDa multienzyme complex that couples two carboxylation reactions, transferring CO(2)(-) from methylmalonyl-CoA to pyruvate, yielding propionyl-CoA and oxaloacetate. The 1.9 A resolution crystal structure of the central 12S hexameric core, which catalyzes the first carboxylation reaction, has been solved bound to its substrate methylmalonyl-CoA. Overall, the structure reveals two stacked trimers related by 2-fold symmetry, and a domain duplication in the monomer. In the active site, the labile carboxylate group of methylmalonyl-CoA is stabilized by interaction with the N-termini of two alpha-helices. The 12S domains are structurally similar to the crotonase/isomerase superfamily, although only domain 1 of each 12S monomer binds ligand. The 12S reaction is similar to that of human propionyl-CoA carboxylase, whose beta-subunit has 50% sequence identity with 12S. A homology model of the propionyl-CoA carboxylase beta-subunit, based on this 12S crystal structure, provides new insight into the propionyl-CoA carboxylase mechanism, its oligomeric structure and the molecular basis of mutations responsible for enzyme deficiency in propionic acidemia.

PubMed: 12743028
DOI: 10.1093/emboj/cdg244

実験手法

X-RAY DIFFRACTION (2 Å)