4FWK

Crystal structure of Salmonella typhimurium propionate kinase (TdcD) in complex with AMP

Summary for 4FWK

• Entry DOI: 10.2210/pdb4fwk/pdb
• Related: 1X3M 1X3N 2E1Y 2E1Z 2E20 4FWL 4FWM 4FWN 4FWO 4FWP 4FWQ 4FWR 4FWS
• Descriptor: Propionate kinase, 1,2-ETHANEDIOL, ADENOSINE MONOPHOSPHATE, ... (4 entities in total)
• Functional Keywords: transferase, kinase, acetate and sugar kinases/hsc70/actin (askha) superfamily, propionate kinase, tdcd, amp, short-chain fatty acid
• Biological source: Salmonella typhimurium
• Total number of polymer chains: 1
• Total formula weight: 45655.69

Authors

Chittori, S.,Savithri, H.S.,Murthy, M.R.N. (deposition date: 2012-07-01, release date: 2013-06-19, Last modification date: 2023-11-08)

Primary citation

Chittori, S.,Simanshu, D.K.,Banerjee, S.,Murthy, A.M.V.,Mathivanan, S.,Savithri, H.S.,Murthy, M.R.N.
Mechanistic features of Salmonella typhimurium propionate kinase (TdcD): insights from kinetic and crystallographic studies.
Biochim.Biophys.Acta, 1834:2036-2044, 2013

PubMed Abstract: Short-chain fatty acids (SCFAs) play a major role in carbon cycle and can be utilized as a source of carbon and energy by bacteria. Salmonella typhimurium propionate kinase (StTdcD) catalyzes reversible transfer of the γ-phosphate of ATP to propionate during l-threonine degradation to propionate. Kinetic analysis revealed that StTdcD possesses broad ligand specificity and could be activated by various SCFAs (propionate>acetate≈butyrate), nucleotides (ATP≈GTP>CTP≈TTP; dATP>dGTP>dCTP) and metal ions (Mg(2+)≈Mn(2+)>Co(2+)). Inhibition of StTdcD by tricarboxylic acid (TCA) cycle intermediates such as citrate, succinate, α-ketoglutarate and malate suggests that the enzyme could be under plausible feedback regulation. Crystal structures of StTdcD bound to PO4 (phosphate), AMP, ATP, Ap4 (adenosine tetraphosphate), GMP, GDP, GTP, CMP and CTP revealed that binding of nucleotide mainly involves hydrophobic interactions with the base moiety and could account for the broad biochemical specificity observed between the enzyme and nucleotides. Modeling and site-directed mutagenesis studies suggest Ala88 to be an important residue involved in determining the rate of catalysis with SCFA substrates. Molecular dynamics simulations on monomeric and dimeric forms of StTdcD revealed plausible open and closed states, and also suggested role for dimerization in stabilizing segment 235-290 involved in interfacial interactions and ligand binding. Observation of an ethylene glycol molecule bound sufficiently close to the γ-phosphate in StTdcD complexes with triphosphate nucleotides supports direct in-line phosphoryl transfer.

PubMed: 23747922
DOI: 10.1016/j.bbapap.2013.05.020

Experimental method

X-RAY DIFFRACTION (2.8 Å)