1Z6B

Crystal structure of Plasmodium falciparum FabZ at 2.1 A

Summary for 1Z6B

• Entry DOI: 10.2210/pdb1z6b/pdb
• Descriptor: fatty acid synthesis protein, CHLORIDE ION, CACODYLATE ION, ... (5 entities in total)
• Functional Keywords: plasmodium falciparum, malaria, beta-hydroxyacyl-acp dehydratase, fatty acid biosynthesis, sad phasing, lyase
• Biological source: Plasmodium falciparum (malaria parasite P. falciparum)
• Total number of polymer chains: 6
• Total formula weight: 103940.52

Authors

Kostrewa, D.,Winkler, F.K.,Folkers, G.,Scapozza, L.,Perozzo, R. (deposition date: 2005-03-22, release date: 2005-06-14, Last modification date: 2024-03-13)

Primary citation

Kostrewa, D.,Winkler, F.K.,Folkers, G.,Scapozza, L.,Perozzo, R.
The crystal structure of PfFabZ, the unique beta-hydroxyacyl-ACP dehydratase involved in fatty acid biosynthesis of Plasmodium falciparum
PROTEIN SCI., 14:1570-1580, 2005

PubMed Abstract: The unique beta-hydroxyacyl-ACP dehydratase in Plasmodium falciparum, PfFabZ, is involved in fatty acid biosynthesis and catalyzes the dehydration of beta-hydroxy fatty acids linked to acyl carrier protein. The structure was solved by single anomalous dispersion (SAD) phasing using a quick-soaking experiment with potassium iodide and refined to a resolution of 2.1 A. The crystal structure represents the first structure of a Plasmodium beta-hydroxyacyl-ACP dehydratase with broad substrate specificity. The asymmetric unit contains a hexamer that appears as a trimer of dimers. Each dimer shows the known "hot dog" fold that has been observed in only a few other protein structures. Each of the two independent active sites in the dimer is formed by equal contributions from both subunits. The active site is mainly hydrophobic and looks like an L-shaped tunnel. The catalytically important amino acids His 133 and Glu 147' (from the other subunit), together with His98', form the only hydrophilic site in this tunnel. The inner end of the active site tunnel is closed by the phenyl ring of Phe 169, which is located in a flexible, partly visible loop. In order to explain the acceptance of substrates longer than ~C-7, the phenyl ring must move away to open the tunnel. The present structure supports an enzymatic mechanism consisting of an elimination reaction catalyzed by His 133 and Glu147'. 3-decynoyl-N-acetylcysteamine, an inhibitor known to interact with the E. coli dehydratase/isomerase, turned out to interact covalently with PfFabZ. A first model of PfFabZ with this potent inhibitor is presented.

PubMed: 15930004
DOI: 10.1110/ps.051373005

Experimental method

X-RAY DIFFRACTION (2.09 Å)