1ZEB

X-ray structure of alkaline phosphatase from human placenta in complex with 5'-AMP

1ZEB の概要

• エントリーDOI: 10.2210/pdb1zeb/pdb
• 関連するPDBエントリー: 1EW2 1ZED 1ZEF
• 分子名称: Alkaline phosphatase, 2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (6 entities in total)
• 機能のキーワード: alkaline phosphatase, 5'-amp, phosphoserine, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Lipid-anchor, GPI-anchor: P05187
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 53525.72

構造登録者

Llinas, P.,Stura, E.A.,Menez, A.,Kiss, Z.,Stigbrand, T.,Millan, J.L.,Le Du, M.H. (登録日: 2005-04-18, 公開日: 2005-06-28, 最終更新日: 2024-10-16)

主引用文献

Llinas, P.,Stura, E.A.,Menez, A.,Kiss, Z.,Stigbrand, T.,Millan, J.L.,Le Du, M.H.
Structural Studies of Human Placental Alkaline Phosphatase in Complex with Functional Ligands.
J.Mol.Biol., 350:441-451, 2005

PubMed Abstract: The activity of human placental alkaline phosphatase (PLAP) is downregulated by a number of effectors such as l-phenylalanine, an uncompetitive inhibitor, 5'-AMP, an antagonist of the effects of PLAP on fibroblast proliferation and by p-nitrophenyl-phosphonate (PNPPate), a non-hydrolysable substrate analogue. For the first two, such regulation may be linked to its biological function that requires a reduced and better-regulated hydrolytic rate. To understand how such disparate ligands are able to inhibit the enzyme, we solved the structure of the complexes at 1.6A, 1.9A and 1.9A resolution, respectively. These crystal structures are the first of an alkaline phosphatase in complex with organic inhibitors. Of the three inhibitors, only l-Phe and PNPPate bind at the active site hydrophobic pocket, providing structural data on the uncompetitive inhibition process. In contrast, all three ligands interact at a remote peripheral site located 28A from the active site. In order to extend these observations to the other members of the human alkaline phosphatase family, we have modelled the structures of the other human isozymes and compared them to PLAP. This comparison highlights the crucial role played by position 429 at the active site in the modulation of the catalytic process, and suggests that the peripheral binding site may be involved in the functional specialization of the PLAP isozyme.

PubMed: 15946677
DOI: 10.1016/j.jmb.2005.04.068

実験手法

X-RAY DIFFRACTION (1.9 Å)