4FWN

Crystal structure of Salmonella typhimurium propionate kinase (TdcD) in complex with Adenosine Tetraphosphate (AP4)

4FWN の概要

• エントリーDOI: 10.2210/pdb4fwn/pdb
• 関連するPDBエントリー: 1X3M 1X3N 2E1Y 2E1Z 2E20 4FWK 4FWL 4FWM 4FWO 4FWP 4FWQ 4FWR 4FWS
• 分子名称: Propionate kinase, 1,2-ETHANEDIOL, ADENOSINE-5'-TETRAPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: transferase, kinase, acetate and sugar kinases/hsc70/actin (askha) superfamily, propionate kinase, tdcd, adenosine tetraphosphate (ap4), short-chain fatty acid
• 由来する生物種: Salmonella typhimurium
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45957.69

構造登録者

Chittori, S.,Savithri, H.S.,Murthy, M.R.N. (登録日: 2012-07-01, 公開日: 2013-06-19, 最終更新日: 2023-11-08)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3 Å)