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- Title
Crystal structure of dimeric FabZ of Plasmodium falciparum reveals conformational switching to active hexamers by peptide flips
- Authors
Swarnamukhi, P. Lakshmi; Sharma, Shailendra Kumar; Bajaj, Preeti; Surolia, Namita; Surolia, Avadhesha; Suguna, Kaza
- Abstract
Abstract: The crystal structure of β-hydroxyacyl acyl carrier protein dehydratase of Plasmodium falciparum (PfFabZ) has been determined at a resolution of 2.4Å. PfFabZ has been found to exist as a homodimer (d-PfFabZ) in the crystals of the present study in contrast to the reported hexameric form (h-PfFabZ) which is a trimer of dimers crystallized in a different condition. The catalytic sites of this enzyme are located in deep narrow tunnel-shaped pockets formed at the dimer interface. A histidine residue from one subunit of the dimer and a glutamate residue from the other subunit lining the tunnel form the catalytic dyad in the reported crystal structures. While the position of glutamate remains unaltered in the crystal structure of d-PfFabZ compared to that in h-PfFabZ, the histidine residue takes up an entirely different conformation and moves away from the tunnel leading to a His-Phe cis–trans peptide flip at the histidine residue. In addition, a loop in the vicinity has been observed to undergo a similar flip at a Tyr–Pro peptide bond. These alterations not only prevent the formation of a hexamer but also distort the active site geometry resulting in a dimeric form of FabZ that is incapable of substrate binding. The dimeric state and an altered catalytic site architecture make d-PfFabZ distinctly different from the FabZ structures described so far. Dynamic light scattering and size exclusion chromatographic studies clearly indicate a pH-related switching of the dimers to active hexamers.
- Subjects
PLASMODIUM falciparum; CARRIER proteins; PSEUDOMONAS aeruginosa; ESCHERICHIA coli
- Publication
FEBS Letters, 2006, Vol 580, Issue 11, p2653
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2006.04.014