2BQ8

Crystal structure of human purple acid phosphatase with an inhibitory conformation of the repression loop

2BQ8 の概要

• エントリーDOI: 10.2210/pdb2bq8/pdb
• 関連するPDBエントリー: 2BQ8
• 分子名称: TARTRATE-RESISTANT ACID PHOSPHATASE TYPE 5, FE (II) ION, ZINC ION, ... (5 entities in total)
• 機能のキーワード: metallophosphatase, dinuclear metal site, trap, hydrolase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34650.13

構造登録者

Straeter, N.,Jasper, B.,Krebs, B. (登録日: 2005-04-27, 公開日: 2005-10-24, 最終更新日: 2024-10-23)

主引用文献

Strater, N.,Jasper, B.,Scholte, M.,Krebs, B.,Duff, A.P.,Langley, D.B.,Han, R.,Averill, B.A.,Freeman, H.C.,Guss, J.M.
Crystal Structures of Recombinant Human Purple Acid Phosphatase with and without an Inhibitory Conformation of the Repression Loop.
J.Mol.Biol., 351:233-, 2005

PubMed Abstract: The crystal structure of human purple acid phosphatase recombinantly expressed in Escherichia coli (rHPAP(Ec)) and Pichia pastoris (rHPAP(Pp)) has been determined in two different crystal forms, both at 2.2A resolution. In both cases, the enzyme crystallized in its oxidized (inactive) state, in which both Fe atoms in the dinuclear active site are Fe(III). The main difference between the two structures is the conformation of the enzyme "repression loop". Proteolytic cleavage of this loop in vivo or in vitro results in significant activation of the mammalian PAPs. In the crystals obtained from rHPAP(Ec), the carboxylate side-chain of Asp145 of this loop acts as a bidentate ligand that bridges the two metal atoms, in a manner analogous to a possible binding mode for a phosphate ester substrate in the enzyme-substrate complex. The carboxylate side-chain of Asp145 and the neighboring Phe146 side-chain thus block the active site, thereby inactivating the enzyme. In the crystal structure of rHPAP(Pp), the enzyme "repression loop" has an open conformation similar to that observed in other mammalian PAP structures. The present structures demonstrate that the repression loop exhibits significant conformational flexibility, and the observed alternate binding mode suggests a possible inhibitory role for this loop.

PubMed: 15993892
DOI: 10.1016/J.JMB.2005.04.014

実験手法

X-RAY DIFFRACTION (2.2 Å)