2ZOG

Crystal structure of mouse carnosinase CN2 complexed with ZN and bestatin

2ZOG の概要

• エントリーDOI: 10.2210/pdb2zog/pdb
• 関連するPDBエントリー: 2ZOG
• 分子名称: Cytosolic non-specific dipeptidase, ZINC ION, 2-(3-AMINO-2-HYDROXY-4-PHENYL-BUTYRYLAMINO)-4-METHYL-PENTANOIC ACID, ... (4 entities in total)
• 機能のキーワード: metallopeptidase, protein-inhibitor complex, cndp2, cndp dipeptidase 2, cn2, bestatin, l-carnosine, carnosinase, zn, carboxypeptidase, hydrolase, metal-binding, metalloprotease, protease, zinc
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cytoplasm (By similarity): Q9D1A2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 107315.37

構造登録者

Unno, H.,Yamashita, T.,Okumura, N.,Kusunoki, M. (登録日: 2008-05-14, 公開日: 2008-06-10, 最終更新日: 2024-03-13)

主引用文献

Unno, H.,Yamashita, T.,Ujita, S.,Okumura, N.,Otani, H.,Okumura, A.,Nagai, K.,Kusunoki, M.
Structural basis for substrate recognition and hydrolysis by mouse carnosinase CN2.
J.Biol.Chem., 283:27289-27299, 2008

PubMed Abstract: L-carnosine is a bioactive dipeptide (beta-alanyl-L-histidine) present in mammalian tissues, including the central nervous system, and has potential neuroprotective and neurotransmitter functions. In mammals, two types of L-carnosine-hydrolyzing enzymes (CN1 and CN2) have been cloned thus far, and they have been classified as metallopeptidases of the M20 family. The enzymatic activity of CN2 requires Mn(2+), and CN2 is inhibited by a nonhydrolyzable substrate analog, bestatin. Here, we present the crystal structures of mouse CN2 complexed with bestatin together with Zn(2+) at a resolution of 1.7 A and that with Mn(2+) at 2.3 A CN2 is a homodimer in a noncrystallographic asymmetric unit, and the Mn(2+) and Zn(2+) complexes closely resemble each other in the overall structure. Each subunit is composed of two domains: domain A, which is complexed with bestatin and two metal ions, and domain B, which provides the major interface for dimer formation. The bestatin molecule bound to domain A interacts with several residues of domain B of the other subunit, and these interactions are likely to be essential for enzyme activity. Since the bestatin molecule is not accessible to the bulk water, substrate binding would require conformational flexibility between domains A and B. The active site structure and substrate-binding model provide a structural basis for the enzymatic activity and substrate specificity of CN2 and related enzymes.

PubMed: 18550540
DOI: 10.1074/jbc.M801657200

実験手法

X-RAY DIFFRACTION (1.7 Å)