6byf

Crystal structure of the core catalytic domain of PP-IP phosphatase SIW14 from S. cerevisiae in complex with citrate

spinqualitylabelsall models 6byf, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6byf is a 9 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.35Å Ligands: CIT, CL, EDO, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SIW14_YEAST Plays a role in actin filament organization and endocytosis. Publication Abstract from PubMed Inositol pyrophosphates (PP-InsPs) are 'energetic' intracellular signals that are ubiquitous in animals, plant and fungi; structural and biochemical characterization of PP-InsP metabolic enzymes provides insight into their evolution, reaction mechanisms, and regulation. Here, we describe the 2.35 A resolution structure of the catalytic core of Siw14, a 5-PP-InsP phosphatase from Saccharomyces cerevisiae, and a member of the protein tyrosinephosphatase (PTP) superfamily. Conclusions that we derive from structural data are supported by extensive site-directed mutagenesis and kinetic analyses, thereby attributing new functional significance to several key residues. We demonstrate the high activity and exquisite specificity of Siw14 for the 5-diphosphate group of PP-InsPs. The three structural elements that demarcate a 9.2 A deep substrate-binding pocket each have spatial equivalents in PTPs, but we identify how these are specialized for Siw14 to bind and hydrolyze the intensely negatively-charged PP-InsPs: (a), the catalytic P-loop with the Cx5RT/S PTP-motif contains additional, positively charged residues; (b), a loop between the alpha5 and alpha6 helices, corresponding to the Q-loop in PTPs, contains a lysine and an arginine that e xtend into the catalytic pocket due to displacement of the alpha5 helix orientation through intramolecular crowding caused by three bulky, hydrophobic residues; (c), the general acid loop in PTPs is replaced in Siw14 with a flexible loop that does not use an aspartate or glutamate as a general-acid. We propose that an acidic residue is not required for phosphoanhydride hydrolysis. Structural and biochemical characterization of Siw14: a protein-tyrosine phosphatase fold that metabolizes inositol pyrophosphates.,Wang H, Gu C, Rolfes RJ, Jessen HJ, Shears SB J Biol Chem. 2018 Mar 14. pii: RA117.001670. doi: 10.1074/jbc.RA117.001670. PMID:29540476 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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