6WRY

CRYSTAL STRUCTURE OF INOSITOL POLYPHOSPHATE 1-PHOSPHATASE INPP1 IN COMPLEX GADOLINIUM AFTER ADDITION OF INOSITOL 1,3,4-TRISPHOSPHATE AT 2.5 ANGSTROM RESOLUTION

Summary for 6WRY

• Entry DOI: 10.2210/pdb6wry/pdb
• Descriptor: Inositol polyphosphate 1-phosphatase, SULFATE ION, GADOLINIUM ATOM, ... (4 entities in total)
• Functional Keywords: inositol phosphate, neurological disease, bipolar disorder, manic depressive illness, phosphatase, signaling protein
• Biological source: Bos taurus (Bovine)
• Total number of polymer chains: 1
• Total formula weight: 43552.58

Authors

Dollins, D.R.,Endo-Streeter, S.,York, J.D. (deposition date: 2020-04-30, release date: 2020-11-25, Last modification date: 2023-10-18)

Primary citation

Dollins, D.E.,Xiong, J.P.,Endo-Streeter, S.,Anderson, D.E.,Bansal, V.S.,Ponder, J.W.,Ren, Y.,York, J.D.
A structural basis for lithium and substrate binding of an inositide phosphatase.
J.Biol.Chem., 296:100059-100059, 2020

PubMed Abstract: 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 with 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 and substrate recognition and define a sequence motif for metal binding within this family of regulatory phosphatases.

PubMed: 33172890
DOI: 10.1074/jbc.RA120.014057

Experimental method

X-RAY DIFFRACTION (2.8 Å)