1on3 | pdb_00001on3
Transcarboxylase 12S crystal structure: hexamer assembly and substrate binding to a multienzyme core (with methylmalonyl-coenzyme a and methylmalonic acid bound)
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| 1on3, resolution 1.90Å | |||||||||||||
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| Ligands: | CD, MCA, DXX and MPD | ||||||||||||
| Activity: | Methylmalonyl-CoA carboxytransferase, with EC number 2.1.3.1 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
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.
About this Structure
1ON3 is a Single protein structure of sequence from Propionibacterium freudenreichii. Full crystallographic information is available from OCA.
Reference
Transcarboxylase 12S crystal structure: hexamer assembly and substrate binding to a multienzyme core., Hall PR, Wang YF, Rivera-Hainaj RE, Zheng X, Pustai-Carey M, Carey PR, Yee VC, EMBO J. 2003 May 15;22(10):2334-47. PMID:12743028
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