8VJW

Structure of Human Neurolysin in complex with angiotensin I peptide

8VJW の概要

• エントリーDOI: 10.2210/pdb8vjw/pdb
• 分子名称: Neurolysin, mitochondrial, Angiotensin-1 peptide N-terminal end, Angiotensin-1 peptide C-terminal end, ... (5 entities in total)
• 機能のキーワード: metallopeptidase, bioactive peptides, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 155990.92

構造登録者

Shi, K.,Aihara, H. (登録日: 2024-01-08, 公開日: 2024-08-21, 最終更新日: 2024-09-25)

主引用文献

Shi, K.,Bagchi, S.,Bickel, J.,Esfahani, S.H.,Yin, L.,Cheng, T.,Karamyan, V.T.,Aihara, H.
Structural basis of divergent substrate recognition and inhibition of human neurolysin.
Sci Rep, 14:18420-18420, 2024

PubMed Abstract: A zinc metallopeptidase neurolysin (Nln) processes diverse bioactive peptides to regulate signaling in the mammalian nervous system. To understand how Nln interacts with various peptides with dissimilar sequences, we determined crystal structures of Nln in complex with diverse peptides including dynorphins, angiotensin, neurotensin, and bradykinin. The structures show that Nln binds these peptides in a large dumbbell-shaped interior cavity constricted at the active site, making minimal structural changes to accommodate different peptide sequences. The structures also show that Nln readily binds similar peptides with distinct registers, which can determine whether the peptide serves as a substrate or a competitive inhibitor. We analyzed the activities and binding of Nln toward various forms of dynorphin A peptides, which highlights the promiscuous nature of peptide binding and shows how dynorphin A (1-13) potently inhibits the Nln activity while dynorphin A (1-8) is efficiently cleaved. Our work provides insights into the broad substrate specificity of Nln and may aid in the future design of small molecule modulators for Nln.

PubMed: 39117724
DOI: 10.1038/s41598-024-67639-w

実験手法

X-RAY DIFFRACTION (2.491 Å)