6A0E

Crystal structure of human protein N-terminal asparagine amidohydrolase (NTAN1)

6A0E の概要

• エントリーDOI: 10.2210/pdb6a0e/pdb
• 分子名称: Protein N-terminal asparagine amidohydrolase, GLYCEROL, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: amidohydrolase, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 72144.03

構造登録者

Park, J.S.,Han, B.W. (登録日: 2018-06-05, 公開日: 2019-12-11, 最終更新日: 2024-10-16)

主引用文献

Park, J.S.,Lee, J.Y.,Nguyen, Y.T.K.,Kang, N.W.,Oh, E.K.,Jang, D.M.,Kim, H.J.,Kim, D.D.,Han, B.W.
Structural Analyses on the Deamidation of N-Terminal Asn in the Human N-Degron Pathway.
Biomolecules, 10:-, 2020

PubMed Abstract: The N-degron pathway is a proteolytic system in which a single N-terminal amino acid acts as a determinant of protein degradation. Especially, degradation signaling of N-terminal asparagine (Nt-Asn) in eukaryotes is initiated from its deamidation by N-terminal asparagine amidohydrolase 1 (NTAN1) into aspartate. Here, we have elucidated structural principles of deamidation by human NTAN1. NTAN1 adopts the characteristic scaffold of CNF1/YfiH-like cysteine hydrolases that features an α-β-β sandwich structure and a catalytic triad comprising Cys, His, and Ser. In vitro deamidation assays using model peptide substrates with varying lengths and sequences showed that NTAN1 prefers hydrophobic residues at the second-position. The structures of NTAN1-peptide complexes further revealed that the recognition of Nt-Asn is sufficiently organized to produce high specificity, and the side chain of the second-position residue is accommodated in a hydrophobic pocket adjacent to the active site of NTAN1. Collectively, our structural and biochemical analyses of the substrate specificity of NTAN1 contribute to understanding the structural basis of all three amidases in the eukaryotic N-degron pathway.

PubMed: 31968674
DOI: 10.3390/biom10010163

実験手法

X-RAY DIFFRACTION (1.947 Å)