1Q7L

Zn-binding domain of the T347G mutant of human aminoacylase-I

1Q7L の概要

• エントリーDOI: 10.2210/pdb1q7l/pdb
• 分子名称: Aminoacylase-1, ZINC ION, GLYCINE, ... (5 entities in total)
• 機能のキーワード: aminoacylase-1, catalysis, enzyme dimerization, site-directed mutagenesis, structure comparison, zinc, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: Q03154 Q03154
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 65109.28

構造登録者

Lindner, H.A.,Lunin, V.V.,Alary, A.,Hecker, R.,Cygler, M.,Menard, R. (登録日: 2003-08-19, 公開日: 2004-01-20, 最終更新日: 2024-02-14)

主引用文献

Lindner, H.A.,Lunin, V.V.,Alary, A.,Hecker, R.,Cygler, M.,Menard, R.
Essential roles of zinc ligation and enzyme dimerization for catalysis in the aminoacylase-1/M20 family.
J.Biol.Chem., 278:44496-44504, 2003

PubMed Abstract: Members of the aminoacylase-1 (Acy1)/M20 family of aminoacylases and exopeptidases exist as either monomers or homodimers. They contain a zinc-binding domain and a second domain mediating dimerization in the latter case. The roles that both domains play in catalysis have been investigated for human Acy1 (hAcy1) by x-ray crystallography and by site-directed mutagenesis. Structure comparison of the dinuclear zinc center in a mutant of hAcy1 reported here with dizinc centers in related enzymes points to a difference in zinc ligation in the Acy1/M20 family. Mutational analysis supports catalytic roles of zinc ions, a vicinal glutamate, and a histidine from the dimerization domain. By complementing different active site mutants of hAcy1, we show that catalysis occurs at the dimer interface. Reinterpretation of the structure of a monomeric homolog, peptidase V, reveals that a domain insertion mimics dimerization. We conclude that monomeric and dimeric Acy1/M20 family members share a unique active site architecture involving both enzyme domains. The study may provide means to improve homologous carboxypeptidase G2 toward application in antibody-directed enzyme prodrug therapy.

PubMed: 12933810
DOI: 10.1074/jbc.M304233200

実験手法

X-RAY DIFFRACTION (1.4 Å)