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- PDB-7lex: Trimeric human Arginase 1 in complex with mAb1 - 2 hArg:3 mAb1 complex -
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Open data
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Basic information
Entry | Database: PDB / ID: 7lex | ||||||
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Title | Trimeric human Arginase 1 in complex with mAb1 - 2 hArg:3 mAb1 complex | ||||||
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![]() | HYDROLASE/IMMUNE SYSTEM / Arginase / Metalloenzyme / IMMUNE SYSTEM / HYDROLASE-IMMUNE SYSTEM complex | ||||||
Function / homology | ![]() positive regulation of neutrophil mediated killing of fungus / Urea cycle / negative regulation of T-helper 2 cell cytokine production / arginase / arginase activity / arginine catabolic process to ornithine / negative regulation of type II interferon-mediated signaling pathway / urea cycle / defense response to protozoan / negative regulation of activated T cell proliferation ...positive regulation of neutrophil mediated killing of fungus / Urea cycle / negative regulation of T-helper 2 cell cytokine production / arginase / arginase activity / arginine catabolic process to ornithine / negative regulation of type II interferon-mediated signaling pathway / urea cycle / defense response to protozoan / negative regulation of activated T cell proliferation / arginine catabolic process / negative regulation of T cell proliferation / specific granule lumen / azurophil granule lumen / manganese ion binding / adaptive immune response / innate immune response / Neutrophil degranulation / extracellular space / extracellular region / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||
![]() | Gomez-Llorente, Y. / Scapin, G. / Palte, R.L. | ||||||
![]() | ![]() Title: Cryo-EM structures of inhibitory antibodies complexed with arginase 1 provide insight into mechanism of action. Authors: Rachel L Palte / Veronica Juan / Yacob Gomez-Llorente / Marc Andre Bailly / Kalyan Chakravarthy / Xun Chen / Daniel Cipriano / Ghassan N Fayad / Laurence Fayadat-Dilman / Symon Gathiaka / ...Authors: Rachel L Palte / Veronica Juan / Yacob Gomez-Llorente / Marc Andre Bailly / Kalyan Chakravarthy / Xun Chen / Daniel Cipriano / Ghassan N Fayad / Laurence Fayadat-Dilman / Symon Gathiaka / Heiko Greb / Brian Hall / Mas Handa / Mark Hsieh / Esther Kofman / Heping Lin / J Richard Miller / Nhung Nguyen / Jennifer O'Neil / Hussam Shaheen / Eric Sterner / Corey Strickland / Angie Sun / Shane Taremi / Giovanna Scapin / ![]() 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 ...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. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 757.9 KB | Display | ![]() |
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PDB format | ![]() | 639.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 23293MC ![]() 7leyC ![]() 7lezC ![]() 7lf0C ![]() 7lf1C ![]() 7lf2C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein | Mass: 34779.879 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Antibody | Mass: 50269.605 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Antibody | Mass: 23488.965 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Molecular weight | Value: 0.427 MDa / Experimental value: YES | ||||||||||||||||||||||||||||
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: C-flat-1.2/1.3 | ||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 6 sec. / Electron dose: 45.5 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 1506 |
Image scans | Width: 3838 / Height: 3710 |
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Processing
Software | Name: PHENIX / Version: 1.12_2829: / Classification: refinement | ||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 37385 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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