6WRO

CRYSTAL STRUCTURE OF INOSITOL POLYPHOSPHATE 1-PHOSPHATASE INPP1 IN COMPLEX GADOLINIUM BUT NO LITHIUM AT 3 ANGSTROM RESOLUTION

6WRO の概要

• エントリーDOI: 10.2210/pdb6wro/pdb
• 分子名称: Inositol polyphosphate 1-phosphatase, GADOLINIUM ATOM, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: inositol phosphate, neurological disease, bipolar disorder, manic depressive illness, phosphatase, metal binding, cellular signaling, signaling protein
• 由来する生物種: Bos taurus (Bovine)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44483.56

構造登録者

Dollins, D.E.,Endo-Streeter, S.,York, J.D. (登録日: 2020-04-29, 公開日: 2020-11-18, 最終更新日: 2023-10-18)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3 Å)