7dmu | pdb_00007dmu

Structure of SARS-CoV-2 spike receptor-binding domain complexed with high affinity ACE2 mutant 3N39

spinqualitylabelsall models 7dmu, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7dmu is a 4 chain structure with sequence from Homo sapiens and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Ligands: BMA, MAN, NAG, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ACE2_HUMAN Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses. Publication Abstract from PubMed SARS-CoV-2 has mutated during the global pandemic leading to viral adaptation to medications and vaccinations. Here we describe an engineered human virus receptor, ACE2, by mutagenesis and screening for binding to the receptor binding domain (RBD). Three cycles of random mutagenesis and cell sorting achieved sub-nanomolar affinity to RBD. Our structural data show that the enhanced affinity comes from better hydrophobic packing and hydrogen-bonding geometry at the interface. Additional disulfide mutations caused the fixing of a closed ACE2 conformation to avoid off-target effects of protease activity, and also improved structural stability. Our engineered ACE2 neutralized SARS-CoV-2 at a 100-fold lower concentration than wild type; we also report that no escape mutants emerged in the co-incubation after 15 passages. Therapeutic administration of engineered ACE2 protected hamsters from SARS-CoV-2 infection, decreased lung virus titers and pathology. Our results provide evidence of a therapeutic potential of engineered ACE2. Engineered ACE2 receptor therapy overcomes mutational escape of SARS-CoV-2.,Higuchi Y, Suzuki T, Arimori T, Ikemura N, Mihara E, Kirita Y, Ohgitani E, Mazda O, Motooka D, Nakamura S, Sakai Y, Itoh Y, Sugihara F, Matsuura Y, Matoba S, Okamoto T, Takagi J, Hoshino A Nat Commun. 2021 Jun 21;12(1):3802. doi: 10.1038/s41467-021-24013-y. PMID:34155214 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Angiotensin-Converting Enzyme 3D structures

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