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Crystal structure of Salmonella typhimurium 2-methylisocitrate lyase (PrpB) and its complex with pyruvate and $Mg^{2+}$

Simanshu, Dhirendra K and Satheshkumar, PS and Savithri, HS and Murthy, MRN (2003) Crystal structure of Salmonella typhimurium 2-methylisocitrate lyase (PrpB) and its complex with pyruvate and $Mg^{2+}$. In: Biochemical and Biophysical Research Communications, 311 (1). pp. 193-201.

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Propionate metabolism in Salmonella typhimurium occurs via 2-methylcitric acid cycle. The last step of this cycle, the cleavage of 2-methylisocitrate to succinate and pyruvate, is catalysed by 2-methylisocitrate lyase (PrpB). Here we report the X-ray crystal structure of the native and the pyruvate/$Mg^{2+}$ bound PrpB from S. typhimurium, determined at 2.1 and 2.3 Å, respectively. The structure closely resembles that of the Escherichia coli enzyme. Unlike the E. coli PrpB, $Mg^{2+}$ could not be located in the native Salmonella PrpB. Only in pyruvate bound PrpB structure, $Mg^{2+}$ was found coordinated with pyruvate. Binding of pyruvate to PrpB seems to induce movement of the $Mg^{2+}$ by 2.5 Å from its position found in E. coli native PrpB. In both the native enzyme and pyruvate/$Mg^{2+}$ bound forms, the active site loop is completely disordered. Examination of the pocket in which pyruvate and glyoxalate bind to 2-methylisocitrate lyase and isocitrate lyase, respectively, reveals plausible rationale for different substrate specificities of these two enzymes. Structural similarities in substrate and metal atom binding site as well as presence of similar residues in the active site suggest possible similarities in the reaction mechanism.

Item Type: Journal Article
Publication: Biochemical and Biophysical Research Communications
Publisher: Elsevier
Additional Information: The Copyright belongs to Elsevier.
Keywords: Salmonella typhimurium;2-Methylisocitrate lyase;Helix swapping;Propionate metabolism;Isocitrate lyase;Crystal structure
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Division of Biological Sciences > Biochemistry
Date Deposited: 19 Nov 2007
Last Modified: 19 Sep 2010 04:26
URI: http://eprints.iisc.ac.in/id/eprint/6589

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