3R9A

Human alanine-glyoxylate aminotransferase in complex with the TPR domain of human PEX5P

「3IMZ」から置き換えられました

3R9A の概要

• エントリーDOI: 10.2210/pdb3r9a/pdb
• 分子名称: Serine--pyruvate aminotransferase, Peroxisomal targeting signal 1 receptor, 2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• 機能のキーワード: tpr-domain, protein-protein complex, peroxisome, aminotransf pyruvate, transferase, disease mutation, membrane, peroxiso biogenesis disorder, protein transport, tpr repeat, transpo zellweger syndrome, transferase-transport protein complex, mitochondrion, pyridoxal phosphate, transferase/transport protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Peroxisome: P21549; Cytoplasm: P50542
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 159308.73

構造登録者

Fodor, K.,Wilmanns, M. (登録日: 2011-03-25, 公開日: 2011-05-11, 最終更新日: 2012-05-02)

主引用文献

Fodor, K.,Wolf, J.,Erdmann, R.,Schliebs, W.,Wilmanns, M.
Molecular requirements for peroxisomal targeting of alanine-glyoxylate aminotransferase as an essential determinant in primary hyperoxaluria type 1
Plos Biol., 10:e1001309-e1001309, 2012

PubMed Abstract: Alanine-glyoxylate aminotransferase is a peroxisomal enzyme, of which various missense mutations lead to irreversible kidney damage via primary hyperoxaluria type 1, in part caused by improper peroxisomal targeting. To unravel the molecular mechanism of its recognition by the peroxisomal receptor Pex5p, we have determined the crystal structure of the respective cargo-receptor complex. It shows an extensive protein/protein interface, with contributions from residues of the peroxisomal targeting signal 1 and additional loops of the C-terminal domain of the cargo. Sequence segments that are crucial for receptor recognition and hydrophobic core interactions within alanine-glyoxylate aminotransferase are overlapping, explaining why receptor recognition highly depends on a properly folded protein. We subsequently characterized several enzyme variants in vitro and in vivo and show that even minor protein fold perturbations are sufficient to impair Pex5p receptor recognition. We discuss how the knowledge of the molecular parameters for alanine-glyoxylate aminotransferase required for peroxisomal translocation could become useful for improved hyperoxaluria type 1 treatment.

PubMed: 22529745
DOI: 10.1371/journal.pbio.1001309

実験手法

X-RAY DIFFRACTION (2.35 Å)