9FXH

Crystal structure of cobalt(II)-substituted double mutant Y115E Y117E human Glutaminyl Cyclase

9FXH の概要

• エントリーDOI: 10.2210/pdb9fxh/pdb
• 関連するPDBエントリー: 9FXG
• 分子名称: Glutaminyl-peptide cyclotransferase, COBALT (II) ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: human glutaminyl cyclase, acyltransferase, hqc, cobalt, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 117241.45

構造登録者

Tassone, G.,Pozzi, C.,Mangani, S. (登録日: 2024-07-01, 公開日: 2024-09-04)

主引用文献

Tassone, G.,Pozzi, C.,Mangani, S.
Metal Ion Binding to Human Glutaminyl Cyclase: A Structural Perspective.
Int J Mol Sci, 25:-, 2024

PubMed Abstract: Glutaminyl-peptide cyclotransferases (QCs) convert the N-terminal glutamine or glutamate residues of protein and peptide substrates into pyroglutamate (pE) by releasing ammonia or a water molecule. The N-terminal pE modification protects peptides/proteins against proteolytic degradation by amino- or exopeptidases, increasing their stability. Mammalian QC is abundant in the brain and a large amount of evidence indicates that pE peptides are involved in the onset of neural human pathologies such as Alzheimer's and Huntington's disease and synucleinopathies. Hence, human QC (hQC) has become an intensively studied target for drug development against these diseases. Soon after its characterization, hQC was identified as a Zn-dependent enzyme, but a partial restoration of the enzyme activity in the presence of the Co(II) ion was also reported, suggesting a possible role of this metal ion in catalysis. The present work aims to investigate the structure of demetallated hQC and of the reconstituted enzyme with Zn(II) and Co(II) and their behavior in the presence of known inhibitors. Furthermore, our structural determinations provide a possible explanation for the presence of the mononuclear metal binding site of hQC, despite the presence of the same conserved metal binding motifs present in distantly related dinuclear aminopeptidase enzymes.

PubMed: 39125848
DOI: 10.3390/ijms25158279

実験手法

X-RAY DIFFRACTION (2.3 Å)