3spx

Crystal structure of O-Acetyl Serine Sulfhydrylase from Leishmania donovani

spinqualitylabelsall models 3spx, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3spx is a 1 chain structure with sequence from Leishmania donovani. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.79Å Ligands: CL, LLP, NA, PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G1C2I2_LEIDO Publication Abstract from PubMed Cysteine is a crucial substrate for the synthesis of glutathione and trypanothione, which in turn maintain intracellular redox homeostasis and defend against oxidative stress in the pathogen Leishmania donovani. Here, the identification, sequencing, characterization and crystal structure at 1.79 A resolution of O-acetylserine sulfhydrylase (OASS), a cysteine-biosynthetic pathway enzyme from L. donovani (LdOASS), are reported. It shows binding to the serine acetyltransferase (SAT) C-terminal peptide, indicating that OASS and SAT interact with each other to form a cysteine synthase complex, further confirmed by the structure of LdOASS in complex with SAT C-terminal octapeptide at 1.68 A resolution. Docking and fluorescence binding studies show that almost all SAT C-terminus mimicking tetrapeptides can bind to LdOASS. Some peptides had a higher binding affinity than the native peptide, indicating that SAT-OASS interactions are not sequence-specific. The structure of LdOASS with a designed peptide (DWSI) revealed that LdOASS makes more interactions with the designed peptide than with the native peptide. In almost all known SAT-OASS interactions the SAT C-terminal sequence was shown to contain amino acids with large side chains. Structural comparison with other OASSs revealed that LdOASS has a relatively less open active-site cleft, which may be responsible for its interaction with the smaller-amino-acid-containing C-terminal LdSAT peptide. Biochemical studies confirmed that LdOASS interacts with SATs from Entamoeba histolytica and Brucella abortus, further displaying its sequence-independent and versatile mode of interaction with SATs. This implicates a critical role of the size of the active-site cleft opening in OASS for SAT-OASS interaction and thus cysteine synthase complex formation. The narrow active-site cleft of O-acetylserine sulfhydrylase from Leishmania donovani allows complex formation with serine acetyltransferases with a range of C-terminal sequences.,Raj I, Kumar S, Gourinath S Acta Crystallogr D Biol Crystallogr. 2012 Aug;68(Pt 8):909-19. Epub 2012 Jul 7. PMID:22868756 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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