28kd

ACE2 extracellular domain in complex with the macrocyclic peptide GR3.1.2

spinqualitylabelsall models 28kd, resolution 2.02Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 28kd is a 4 chain structure with sequence from Homo sapiens and Synthetic plasmid. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.02Å Ligands: 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 Macrocyclic peptides (MPs) are valuable molecular formats for drug development, bridging small molecules and larger biologics due to their favorable pharmacological properties. Here, we describe the discovery of low-nanomolar inhibitors of human angiotensin-converting enzyme 2 (hACE2) by quantitatively screening millions of structurally diverse disulfide-cyclized peptide ligands using yeast display technology. The most potent yeast-encoded "one-ring" and "two-ring" MP inhibit hACE2 with K(i) values of 1.9 and 1.5 nM, respectively. These inhibitory potencies are comparable to those of other cyclic peptides discovered using well-established in vitro display technologies. Crystal structures of the two MPs in complex with hACE2 reveal the adoption of either a rigid beta-hairpin or a cysteine-stabilized alpha-helix/alpha-helix motif. Both MPs exhibit binding modes distinct from those of previously reported inhibitors. Thus, yeast display is a valid technology to rapidly generate MPs with desired binding properties for the development of potential therapeutics. Yeast Display Technology Enables Rapid Discovery of Low-Nanomolar Macrocyclic Peptide Inhibitors of Human Angiotensin-Converting Enzyme 2.,Romanyuk Z, Bettin G, Brear P, Linciano S, Mazzocato Y, Bonadies S, Zanotto I, Mazzucco C, Monferone A, Soler MA, Pasut G, Martin S, Scarso A, Heinis C, Rothenberger S, Hyvonen M, Angelini A J Med Chem. 2026 Mar 24. doi: 10.1021/acs.jmedchem.5c02876. PMID:41875055 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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