3FW0

Structure of Peptidyl-alpha-hydroxyglycine alpha-Amidating Lyase (PAL) bound to alpha-hydroxyhippuric acid (non-peptidic substrate)

3FW0 の概要

• エントリーDOI: 10.2210/pdb3fw0/pdb
• 関連するPDBエントリー: 3FVZ
• 分子名称: Peptidyl-glycine alpha-amidating monooxygenase, MERCURY (II) ION, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: beta propeller, zinc, calcium, mercury, lyase, peptide amidation, substrate, hydroxyhippuric acid, alternative splicing, cleavage on pair of basic residues, copper, cytoplasmic vesicle, glycoprotein, membrane, metal-binding, monooxygenase, multifunctional enzyme, oxidoreductase, phosphoprotein, sulfation, transmembrane, vitamin c
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats)
• 細胞内の位置: Cytoplasmic vesicle, secretory vesicle membrane; Single-pass membrane protein: P14925
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37550.52

構造登録者

Chufan, E.E.,De, M.,Eipper, B.A.,Mains, R.E.,Amzel, L.M. (登録日: 2009-01-16, 公開日: 2009-09-01, 最終更新日: 2024-11-06)

主引用文献

Chufan, E.E.,De, M.,Eipper, B.A.,Mains, R.E.,Amzel, L.M.
Amidation of bioactive peptides: the structure of the lyase domain of the amidating enzyme.
Structure, 17:965-973, 2009

PubMed Abstract: Many neuropeptides and peptide hormones require amidation of their carboxy terminal for full biological activity. The enzyme peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL; EC 4.3.2.5) catalyzes the second and last step of this reaction, N-dealkylation of the peptidyl-alpha-hydroxyglycine to generate the alpha-amidated peptide and glyoxylate. Here we report the X-ray crystal structure of the PAL catalytic core (PALcc) alone and in complex with the nonpeptidic substrate alpha-hydroxyhippuric acid. The structures show that PAL folds as a six-bladed beta-propeller. The active site is formed by a Zn(II) ion coordinated by three histidine residues; the substrate binds to this site with its alpha-hydroxyl group coordinated to the Zn(II) ion. The structures also reveal a tyrosine residue (Tyr(654)) at the active site as the catalytic base for hydroxyl deprotonation, an unusual role for tyrosine. A reaction mechanism is proposed based on this structural data and validated by biochemical analysis of site-directed PALcc mutants.

PubMed: 19604476
DOI: 10.1016/j.str.2009.05.008

実験手法

X-RAY DIFFRACTION (2.52 Å)