8TOU
ACE2-peptide 2 complex crystal form 3
Summary for 8TOU
| Entry DOI | 10.2210/pdb8tou/pdb |
| Related | 8TOQ 8TOR 8TOS 8TOT |
| Descriptor | Angiotensin-converting enzyme 2, Cyclic peptide 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | peptidase, enzyme, sars-cov-2, angiotensin, protein binding |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 75509.36 |
| Authors | Franck, C.,Payne, R.J.,Christie, M. (deposition date: 2023-08-04, release date: 2024-02-07, Last modification date: 2024-11-06) |
| Primary citation | Bedding, M.J.,Franck, C.,Johansen-Leete, J.,Aggarwal, A.,Maxwell, J.W.C.,Patel, K.,Hawkins, P.M.E.,Low, J.K.K.,Siddiquee, R.,Sani, H.M.,Ford, D.J.,Turville, S.,Mackay, J.P.,Passioura, T.,Christie, M.,Payne, R.J. Discovery of High Affinity Cyclic Peptide Ligands for Human ACE2 with SARS-CoV-2 Entry Inhibitory Activity. Acs Chem.Biol., 19:141-152, 2024 Cited by PubMed Abstract: The development of effective antiviral compounds is essential for mitigating the effects of the COVID-19 pandemic. Entry of SARS-CoV-2 virions into host cells is mediated by the interaction between the viral spike (S) protein and membrane-bound angiotensin-converting enzyme 2 (ACE2) on the surface of epithelial cells. Inhibition of this viral protein-host protein interaction is an attractive avenue for the development of antiviral molecules with numerous spike-binding molecules generated to date. Herein, we describe an alternative approach to inhibit the spike-ACE2 interaction by targeting the spike-binding interface of human ACE2 via mRNA display. Two consecutive display selections were performed to direct cyclic peptide ligand binding toward the spike binding interface of ACE2. Through this process, potent cyclic peptide binders of human ACE2 (with affinities in the picomolar to nanomolar range) were identified, two of which neutralized SARS-CoV-2 entry. This work demonstrates the potential of targeting ACE2 for the generation of anti-SARS-CoV-2 therapeutics as well as broad spectrum antivirals for the treatment of SARS-like betacoronavirus infection. PubMed: 38085789DOI: 10.1021/acschembio.3c00568 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.1 Å) |
Structure validation
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