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7LF2

Trimeric human Arginase 1 in complex with mAb4

Summary for 7LF2
Entry DOI10.2210/pdb7lf2/pdb
EMDB information23298
DescriptorArginase-1, mAb4 monoclonal antibody heavy chain, mAb4 monoclonal antibody light chain, ... (4 entities in total)
Functional Keywordsarginase, metalloenzyme, immune system, hydrolase-immune system complex, hydrolase/immune system
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains18
Total formula weight643431.71
Authors
Gomez-Llorente, Y.,Scapin, G.,Palte, R.L. (deposition date: 2021-01-15, release date: 2021-09-01, Last modification date: 2024-10-16)
Primary citationPalte, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.72 Å)
Structure validation

237992

数据于2025-06-25公开中

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