7lez | pdb_00007lez

Trimeric human Arginase 1 in complex with mAb1 - 2 hArg:2 mAb1 complex

spinqualitylabelsall models 7lez, resolution 4.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7lez is a 14 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.15Å Ligands: MN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease ARGI1_HUMAN Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:207800; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia. Function ARGI1_HUMAN Publication Abstract from PubMed 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 A 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. Cryo-EM structures of inhibitory antibodies complexed with arginase 1 provide insight into mechanism of action.,Palte RL, Juan V, Gomez-Llorente Y, Bailly MA, Chakravarthy K, Chen X, Cipriano D, Fayad GN, Fayadat-Dilman L, Gathiaka S, Greb H, Hall B, Handa M, Hsieh M, Kofman E, Lin H, Miller JR, Nguyen N, O'Neil J, Shaheen H, Sterner E, Strickland C, Sun A, Taremi S, Scapin G Commun Biol. 2021 Jul 29;4(1):927. doi: 10.1038/s42003-021-02444-z. PMID:34326456 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Arginase 3D structures Monoclonal Antibodies 3D structures

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