7kio

Crystal structure of inositol polyphosphate 1-phosphatase (INPP1) D54A mutant

spinqualitylabelsall models 7kio, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7kio is a 1 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: CA, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function INPP_BOVIN Publication Abstract from PubMed Inositol polyphosphate 1-phosphatase (INPP1) is a prototype member of metal-dependent/lithium-inhibited phosphomonoesterase protein family defined by a conserved three-dimensional core structure. Enzymes within this family function in distinct pathways including: inositide signaling, gluconeogenesis, and sulfur assimilation. Using structural and biochemical studies, we report the effect of substrate and lithium on a network of metal binding sites within the catalytic center of INPP1. We find that lithium preferentially occupies a key site involved in metal-activation only when substrate or product is added. Mutation of a conserved residue that selectively coordinates the putative lithium-binding site results in a dramatic 100-fold reduction in the inhibitory constant as compared to wild-type. Furthermore, we report the INPP1/inositol 1,4-bisphosphate complex which illuminates key features of the enzyme active site. Our results provide insights into a structural basis for uncompetitive lithium inhibition, substrate recognition and define a sequence motif for metal binding within this family of regulatory phosphatases. A Structural Basis for Lithium and Substrate Binding of an Inositide Phosphatase.,Dollins DE, Xiong JP, Endo-Streeter S, Anderson DE, Bansal VS, Ponder JW, Ren Y, York JD J Biol Chem. 2020 Nov 10. pii: RA120.014057. doi: 10.1074/jbc.RA120.014057. PMID:33172890 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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