4O6Z
Crystal structure of serine hydroxymethyltransferase with covalently bound PLP Schiff-base from Plasmodium falciparum
Summary for 4O6Z
| Entry DOI | 10.2210/pdb4o6z/pdb |
| Descriptor | Serine hydroxymethyltransferase, PYRIDOXAL-5'-PHOSPHATE, PHOSPHATE ION, ... (4 entities in total) |
| Functional Keywords | alpha/beta protein, transferase, methyltransferase activity, cytosol |
| Biological source | Plasmodium falciparum |
| Total number of polymer chains | 4 |
| Total formula weight | 217302.49 |
| Authors | Chitnumsub, P.,Jaruwat, A.,Leartsakulpanich, U. (deposition date: 2013-12-24, release date: 2014-06-11, Last modification date: 2023-11-08) |
| Primary citation | Chitnumsub, P.,Ittarat, W.,Jaruwat, A.,Noytanom, K.,Amornwatcharapong, W.,Pornthanakasem, W.,Chaiyen, P.,Yuthavong, Y.,Leartsakulpanich, U. The structure of Plasmodium falciparum serine hydroxymethyltransferase reveals a novel redox switch that regulates its activities. Acta Crystallogr.,Sect.D, 70:1517-1527, 2014 Cited by PubMed Abstract: Plasmodium falciparum serine hydroxymethyltransferase (PfSHMT), an enzyme in the dTMP synthesis cycle, is an antimalarial target because inhibition of its expression or function has been shown to be lethal to the parasite. As the wild-type enzyme could not be crystallized, protein engineering of residues on the surface was carried out. The surface-engineered mutant PfSHMT-F292E was successfully crystallized and its structure was determined at 3 Å resolution. The PfSHMT-F292E structure is a good representation of PfSHMT as this variant revealed biochemical properties similar to those of the wild type. Although the overall structure of PfSHMT is similar to those of other SHMTs, unique features including the presence of two loops and a distinctive cysteine pair formed by Cys125 and Cys364 in the tetrahydrofolate (THF) substrate binding pocket were identified. These structural characteristics have never been reported in other SHMTs. Biochemical characterization and mutation analysis of these two residues confirm that they act as a disulfide/sulfhydryl switch to regulate the THF-dependent catalytic function of the enzyme. This redox switch is not present in the human enzyme, in which the cysteine pair is absent. The data reported here can be further exploited as a new strategy to specifically disrupt the activity of the parasite enzyme without interfering with the function of the human enzyme. PubMed: 24914963DOI: 10.1107/S1399004714005598 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.98 Å) |
Structure validation
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