Crystal structures of Salmonella typhimurium propionate kinase and its complex with $A{p_4}A$: Evidence for a novel $A{p_4}A$ synthetic activity

Simanshu, Dhirendra K and Savithri, HS and Murthy, MRN (2008) Crystal structures of Salmonella typhimurium propionate kinase and its complex with $A{p_4}A$: Evidence for a novel $A{p_4}A$ synthetic activity. In: Proteins: Structure, Function, and Bioinformatics, 70 (4). pp. 1379-1388.

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Abstract

Propionate kinase catalyses the last step in the anaerobic breakdown of L-threonine to propionate in which propionyl phosphate and ADP are converted to propionate and ATP. Here we report the structures of propionate kinase (TdcD) in the native form as well as in complex with diadenosine $5^{\prime}$, $5^{{\prime}{\prime}{\prime}}-{P^1}$, $P^4$-tetraphosphate $(A{p_4}A)$ by X-ray crystallography. Structure of TdcD obtained after cocrystallization with ATP showed $Ap_4A$ bound to the active site pocket suggesting the presence of $Ap_4A$ synthetic activity in TdcD. Binding of $Ap_4A$ to the enzyme was confirmed by the structure determination of a TdcD-$A{p_4}A$ complex obtained after cocrystallization of TdcD with commercially available $A{p_4}A$. Mass spectroscopic studies provided further evidence for the formation of $A{p_4}A$ by propionate kinase in the presence of ATP. In the TdcD-$A{p_4}A$ complex structure, $A{p_4}A$ is present in an extended conformation with one adenosine moiety present in the nucleotide binding site and other in the proposed propionate binding site. These observations tend to support direct in-line transfer of phosphoryl group during the kinase reaction.

Item Type: Journal Article Copyright of this article belongs to John Wiley & Sons, Inc. Propionate kinase;$Ap_4A$;propionate;TdcD;diadenosine tetraphosphate;Salmonella typhimurium. Division of Biological Sciences > Molecular Biophysics UnitDivision of Biological Sciences > Biochemistry 17 Oct 2008 10:03 19 Sep 2010 04:50 http://eprints.iisc.ernet.in/id/eprint/16070