+Open data
-Basic information
Entry | Database: PDB / ID: 8b9p | ||||||
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Title | ACE2 in complex with bicyclic peptide inhibitor | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / Cov-2-sars bind proteins | ||||||
Function / homology | Function and homology information positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / positive regulation of gap junction assembly / regulation of vasoconstriction / regulation of cardiac conduction ...positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / positive regulation of gap junction assembly / regulation of vasoconstriction / regulation of cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / angiotensin maturation / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / carboxypeptidase activity / negative regulation of signaling receptor activity / Attachment and Entry / positive regulation of cardiac muscle contraction / regulation of cytokine production / viral life cycle / blood vessel diameter maintenance / brush border membrane / regulation of transmembrane transporter activity / negative regulation of smooth muscle cell proliferation / cilium / negative regulation of ERK1 and ERK2 cascade / metallopeptidase activity / positive regulation of reactive oxygen species metabolic process / endocytic vesicle membrane / virus receptor activity / regulation of cell population proliferation / regulation of inflammatory response / endopeptidase activity / Potential therapeutics for SARS / Induction of Cell-Cell Fusion / entry receptor-mediated virion attachment to host cell / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / receptor-mediated virion attachment to host cell / symbiont entry into host cell / apical plasma membrane / membrane raft / endoplasmic reticulum lumen / cell surface / extracellular space / extracellular exosome / zinc ion binding / extracellular region / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) synthetic construct (others) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.11 Å | ||||||
Authors | Brear, P. / Lulla, A. / Harman, M. / Dods, R. / Chen, L. / Bezerra, G. / Demydchuk, Y. / Stanway, S. / Hyvonen, M. | ||||||
Funding support | 1items
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Citation | Journal: J.Med.Chem. / Year: 2023 Title: Structure-Guided Chemical Optimization of Bicyclic Peptide ( Bicycle ) Inhibitors of Angiotensin-Converting Enzyme 2. Authors: Harman, M.A.J. / Stanway, S.J. / Scott, H. / Demydchuk, Y. / Bezerra, G.A. / Pellegrino, S. / Chen, L. / Brear, P. / Lulla, A. / Hyvonen, M. / Beswick, P.J. / Skynner, M.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8b9p.cif.gz | 259 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8b9p.ent.gz | 206.5 KB | Display | PDB format |
PDBx/mmJSON format | 8b9p.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/b9/8b9p ftp://data.pdbj.org/pub/pdb/validation_reports/b9/8b9p | HTTPS FTP |
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-Related structure data
Related structure data | 8bfwC 8bn1C 8byjC 1r42S S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 70587.188 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACE2, UNQ868/PRO1885 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9BYF1 #2: Protein/peptide | Mass: 1946.373 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) #3: Chemical | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.22 Å3/Da / Density % sol: 44.53 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 4.6 / Details: 0.02 M CaCl2, 0.1 M Na Acet, 30 %v/v MPD |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å |
Detector | Type: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Feb 16, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 2.11→66.69 Å / Num. obs: 72474 / % possible obs: 99 % / Redundancy: 12.8 % / CC1/2: 0.998 / Rmerge(I) obs: 0.136 / Rpim(I) all: 0.039 / Rrim(I) all: 0.142 / Net I/σ(I): 9.2 / Num. measured all: 930470 |
Reflection shell | Resolution: 2.11→2.15 Å / % possible obs: 87 % / Redundancy: 8.3 % / Rmerge(I) obs: 3.797 / Num. measured all: 25810 / Num. unique obs: 3116 / CC1/2: 0.282 / Rpim(I) all: 1.379 / Rrim(I) all: 4.056 / Net I/σ(I) obs: 0.3 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1R42 Resolution: 2.11→66.69 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.934 / SU B: 17.935 / SU ML: 0.378 / Cross valid method: THROUGHOUT / ESU R: 0.296 / ESU R Free: 0.247 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 58.441 Å2
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Refinement step | Cycle: 1 / Resolution: 2.11→66.69 Å
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Refine LS restraints |
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