4FWR: Crystal structure of Salmonella typhimurium propionate kinase (TdcD) in complex with CMP

Citation:
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 gamma-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 approximately butyrate), nucleotides (ATP approximately GTP>CTP approximately TTP; dATP>dGTP>dCTP) and metal ions (Mg(2+) approximately Mn(2+)>Co(2+)). Inhibition of StTdcD by tricarboxylic acid (TCA) cycle intermediates such as citrate, succinate, alpha-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 gamma-phosphate in StTdcD complexes with triphosphate nucleotides supports direct in-line phosphoryl transfer.
PDB ID: 4FWRDownload
MMDB ID: 111032
PDB Deposition Date: 2012/7/1
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Biological Unit for 4FWR: dimeric; determined by author and by software (PISA)
Molecular Components in 4FWR
Label Count Molecule
Proteins (2 molecules)
2
Propionate Kinase(Gene symbol: tdcD)
Molecule annotation
Chemicals (6 molecules)
1
4
2
2
* Click molecule labels to explore molecular sequence information.

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