View source for 7lf2


==Trimeric human Arginase 1 in complex with mAb4==
<StructureSection load='7lf2' size='340' side='right'caption='[[7lf2]], [[Resolution|resolution]] 3.72&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lf2]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LF2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LF2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.72&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7lf2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lf2 OCA], [https://pdbe.org/7lf2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lf2 RCSB], [https://www.ebi.ac.uk/pdbsum/7lf2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lf2 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== 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<ref>PMID:34326456</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lf2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Arginase 3D structures|Arginase 3D structures]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gomez-Llorente Y]]
[[Category: Palte RL]]
[[Category: Scapin G]]