3MRU

Crystal Structure of Aminoacylhistidine Dipeptidase from Vibrio alginolyticus

3MRU の概要

• エントリーDOI: 10.2210/pdb3mru/pdb
• 分子名称: Aminoacyl-histidine dipeptidase, ZINC ION (2 entities in total)
• 機能のキーワード: metalloprotease, homodimer, hydrolase
• 由来する生物種: Vibrio alginolyticus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 107526.97

構造登録者

Chang, C.-Y.,Hsieh, Y.-C.,Wu, T.-K.,Chen, C.-J. (登録日: 2010-04-29, 公開日: 2010-09-01, 最終更新日: 2023-11-01)

主引用文献

Chang, C.-Y.,Hsieh, Y.-C.,Wang, T.-Y.,Chen, Y.-C.,Wang, Y.-K.,Chiang, T.-W.,Chen, Y.-J.,Chang, C.-H.,Chen, C.-J.,Wu, T.-K.
Crystal structure and mutational analysis of aminoacylhistidine dipeptidase from vibrio alginolyticus reveal a new architecture of M20 metallopeptidases
J.Biol.Chem., 285:39500-39510, 2010

PubMed Abstract: Aminoacylhistidine dipeptidases (PepD, EC 3.4.13.3) belong to the family of M20 metallopeptidases from the metallopeptidase H clan that catalyze a broad range of dipeptide and tripeptide substrates, including L-carnosine and L-homocarnosine. Homocarnosine has been suggested as a precursor for the neurotransmitter γ-aminobutyric acid (GABA) and may mediate the antiseizure effects of GABAergic therapies. Here, we report the crystal structure of PepD from Vibrio alginolyticus and the results of mutational analysis of substrate-binding residues in the C-terminal as well as substrate specificity of the PepD catalytic domain-alone truncated protein PepD(CAT). The structure of PepD was found to exist as a homodimer, in which each monomer comprises a catalytic domain containing two zinc ions at the active site center for its hydrolytic function and a lid domain utilizing hydrogen bonds between helices to form the dimer interface. Although the PepD is structurally similar to PepV, which exists as a monomer, putative substrate-binding residues reside in different topological regions of the polypeptide chain. In addition, the lid domain of the PepD contains an "extra" domain not observed in related M20 family metallopeptidases with a dimeric structure. Mutational assays confirmed both the putative di-zinc allocations and the architecture of substrate recognition. In addition, the catalytic domain-alone truncated PepD(CAT) exhibited substrate specificity to l-homocarnosine compared with that of the wild-type PepD, indicating a potential value in applications of PepD(CAT) for GABAergic therapies or neuroprotection.

PubMed: 20819954
DOI: 10.1074/jbc.M110.139683

実験手法

X-RAY DIFFRACTION (3 Å)