7LF0

Trimeric human Arginase 1 in complex with mAb2

7LF0 の概要

• エントリーDOI: 10.2210/pdb7lf0/pdb
• EMDBエントリー: 23296
• 分子名称: Arginase-1, mAb2 heavy chain, mAb2 light chain (3 entities in total)
• 機能のキーワード: arginase, metalloenzyme, immune system, hydrolase-immune system complex, hydrolase/immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 647055.12

構造登録者

Gomez-Llorente, Y.,Scapin, G.,Palte, R.L. (登録日: 2021-01-15, 公開日: 2021-09-01, 最終更新日: 2024-10-23)

主引用文献

Palte, R.L.,Juan, V.,Gomez-Llorente, Y.,Bailly, M.A.,Chakravarthy, K.,Chen, X.,Cipriano, D.,Fayadat-Dilman, L.,Gathiaka, S.,Greb, H.,Hall, B.,Handa, M.,Hsieh, M.,Kofman, E.,Lin, H.,Miller, J.R.,Nguyen, N.,O'Neil, J.,Shaheen, H.,Sterner, E.,Strickland, C.,Sun, A.,Taremi, S.,Scapin, G.
Cryo-EM structures of inhibitory antibodies complexed with arginase 1 provide insight into mechanism of action.
Commun Biol, 4:927-927, 2021

PubMed Abstract: Human Arginase 1 (hArg1) is a metalloenzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea, and modulates T-cell-mediated immune response. Arginase-targeted therapies have been pursued across several disease areas including immunology, oncology, nervous system dysfunction, and cardiovascular dysfunction and diseases. Currently, all published hArg1 inhibitors are small molecules usually less than 350 Da in size. Here we report the cryo-electron microscopy structures of potent and inhibitory anti-hArg antibodies bound to hArg1 which form distinct macromolecular complexes that are greater than 650 kDa. With local resolutions of 3.5 Å or better we unambiguously mapped epitopes and paratopes for all five antibodies and determined that the antibodies act through orthosteric and allosteric mechanisms. These hArg1:antibody complexes present an alternative mechanism to inhibit hArg1 activity and highlight the ability to utilize antibodies as probes in the discovery and development of peptide and small molecule inhibitors for enzymes in general.

PubMed: 34326456
DOI: 10.1038/s42003-021-02444-z

実験手法

ELECTRON MICROSCOPY (3.68 Å)