3q1x

Crystal structure of Entamoeba histolytica serine acetyltransferase 1 in complex with L-serine

spinqualitylabelsall models 3q1x, resolution 1.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3q1x is a 1 chain structure with sequence from Entamoeba histolytica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.59Å Ligands: SER, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9U8X2_ENTHI Publication Abstract from PubMed Cysteine (cys) plays a major role in growth and survival of the human parasite Entamoeba histolytica. We report here the crystal structure of serine acetyltransferase (SAT) isoform1, a cysteine biosynthetic pathway enzyme, from E. histolytica (EhSAT1) at 1.77 [Aring], in complex with its substrate serine (ser) at 1.59 [Aring] and inhibitor cys at 1.78 [Aring] resolution. EhSAT1 exists as a trimer both in solution as well as in crystal structure, unlike hexamers formed by other known SATs. The difference in oligomeric state is due to the N- terminal region of the EhSAT1, which has very low sequence similarity to known structures, also differs in orientation and charge distribution. The ser and cys bind to the same site, confirming that cys is a competitive inhibitor of ser. The disordered C-terminal region and the loop near the active site are responsible for solvent accessible acetyl Co-A binding site and thus lose inhibition to acetyl Co-A by the feedback inhibitor cys. Docking and fluorescence studies show that EhSAT1 C-terminal mimicking peptides can bind to o-acetyl serine sulfhydrylase (EhOASS), while native C-terminal peptide does not show any binding. To test further, C-terminal end of EhSAT1 was mutated and found that it inhibits EhOASS, confirming modified EhSAT1 can bind to EhOASS. The apparent inability of EhSAT1 to form a hexamer and differences in C-terminal region are likely to be the major reasons for the lack of formation of the large cysteine synthase complex and loss of a complex regulatory mechanism in E. histolytica. Structural and biochemical studies of serine acetyltransferase reveal why the parasite Entamoeba histolytica cannot form cysteine synthase complex.,Kumar S, Raj I, Nagpal I, Subbarao N, Gourinath S J Biol Chem. 2011 Feb 5. PMID:21297164 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine acetyltransferase

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