3O8J

Crystal structure of 2-methylcitrate synthase (PrpC) from Salmonella typhimurium

Summary for 3O8J

• Entry DOI: 10.2210/pdb3o8j/pdb
• Related: 1A59 1CTS 1K3P
• Descriptor: 2-methylcitrate synthase, GLYCEROL (3 entities in total)
• Functional Keywords: short chain fatty acids, propionate metabolism, 2-methylcitric acid cycle, prpc or 2-mcs, glta or cs, citrate synthase, 2-methylcitrate synthase, transferase
• Biological source: Salmonella enterica
• Total number of polymer chains: 10
• Total formula weight: 450802.87

Authors

Chittori, S.,Savithri, H.S.,Murthy, M.R.N. (deposition date: 2010-08-03, release date: 2011-04-13, Last modification date: 2023-11-01)

Primary citation

Chittori, S.,Savithri, H.S.,Murthy, M.R.N.
Crystal structure of Salmonella typhimurium 2-methylcitrate synthase: Insights on domain movement and substrate specificity
J.Struct.Biol., 174:58-68, 2011

PubMed Abstract: 2-Methylcitric acid (2-MCA) cycle is one of the well studied pathways for the utilization of propionate as a source of carbon and energy in bacteria such as Salmonella typhimurium and Escherichia coli. 2-Methylcitrate synthase (2-MCS) catalyzes the conversion of oxaloacetate and propionyl-CoA to 2-methylcitrate and CoA in the second step of 2-MCA cycle. Here, we report the X-ray crystal structure of S. typhimurium 2-MCS (StPrpC) at 2.4Å resolution and its functional characterization. StPrpC was found to utilize propionyl-CoA more efficiently than acetyl-CoA or butyryl-CoA. The polypeptide fold and the catalytic residues of StPrpC are conserved in citrate synthases (CSs) suggesting similarities in their functional mechanisms. In the triclinic P1 cell, StPrpC molecules were organized as decamers composed of five identical dimer units. In solution, StPrpC was in a dimeric form at low concentrations and was converted to larger oligomers at higher concentrations. CSs are usually dimeric proteins. In Gram-negative bacteria, a hexameric form, believed to be important for regulation of activity by NADH, is also observed. Structural comparisons with hexameric E. coli CS suggested that the key residues involved in NADH binding are not conserved in StPrpC. Structural comparison with the ligand free and bound states of CSs showed that StPrpC is in a nearly closed conformation despite the absence of bound ligands. It was found that the Tyr197 and Leu324 of StPrpC are structurally equivalent to the ligand binding residues His and Val, respectively, of CSs. These substitutions might determine the specificities for acyl-CoAs of these enzymes.

PubMed: 20970504
DOI: 10.1016/j.jsb.2010.10.008

Experimental method

X-RAY DIFFRACTION (2.41 Å)