[English] 日本語
Yorodumi
- PDB-8byj: The structures of Ace2 in complex with bicyclic peptide inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8byj
TitleThe structures of Ace2 in complex with bicyclic peptide inhibitor
Components
  • ALA-CYS-VAL-ARG-SER-HIS-CYS-SER-SER-LEU-LEU-PRO-ARG-ILE-HIS-CYS-ALA
  • Processed angiotensin-converting enzyme 2
KeywordsMEMBRANE 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 / positive regulation of gap junction assembly / tryptophan transport / regulation of cardiac conduction / regulation of vasoconstriction ...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 / positive regulation of gap junction assembly / tryptophan transport / regulation of cardiac conduction / regulation of vasoconstriction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / angiotensin maturation / Metabolism of Angiotensinogen to Angiotensins / negative regulation of signaling receptor activity / carboxypeptidase activity / Attachment and Entry / positive regulation of cardiac muscle contraction / viral life cycle / regulation of cytokine production / blood vessel diameter maintenance / negative regulation of smooth muscle cell proliferation / brush border membrane / regulation of transmembrane transporter activity / 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 / membrane fusion / Attachment and Entry / receptor-mediated virion attachment to host cell / symbiont entry into host cell / membrane raft / apical plasma membrane / endoplasmic reticulum lumen / cell surface / extracellular space / extracellular exosome / zinc ion binding / extracellular region / identical protein binding / membrane / plasma membrane
Similarity search - Function
Collectrin domain / Renal amino acid transporter / Collectrin-like domain profile. / Peptidase M2, peptidyl-dipeptidase A / Angiotensin-converting enzyme / Peptidase family M2 domain profile. / Neutral zinc metallopeptidases, zinc-binding region signature.
Similarity search - Domain/homology
Chem-LFI / Angiotensin-converting enzyme 2
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.07 Å
AuthorsBrear, P. / Lulla, A. / Harman, M. / Dods, R. / Chen, L. / Bezerra, G. / Demydchuk, Y. / Stanway, S. / Hyvonen, M.
Funding support1items
OrganizationGrant numberCountry
Other private
CitationJournal: 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
DepositionDec 13, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 20, 2023Provider: repository / Type: Initial release
Revision 1.1Nov 20, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Processed angiotensin-converting enzyme 2
B: Processed angiotensin-converting enzyme 2
C: ALA-CYS-VAL-ARG-SER-HIS-CYS-SER-SER-LEU-LEU-PRO-ARG-ILE-HIS-CYS-ALA
D: ALA-CYS-VAL-ARG-SER-HIS-CYS-SER-SER-LEU-LEU-PRO-ARG-ILE-HIS-CYS-ALA
hetero molecules


Theoretical massNumber of molelcules
Total (without water)146,0239
Polymers144,8854
Non-polymers1,1385
Water2,306128
1
A: Processed angiotensin-converting enzyme 2
D: ALA-CYS-VAL-ARG-SER-HIS-CYS-SER-SER-LEU-LEU-PRO-ARG-ILE-HIS-CYS-ALA
hetero molecules


Theoretical massNumber of molelcules
Total (without water)73,0004
Polymers72,4422
Non-polymers5572
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2770 Å2
ΔGint-46 kcal/mol
Surface area25090 Å2
MethodPISA
2
B: Processed angiotensin-converting enzyme 2
C: ALA-CYS-VAL-ARG-SER-HIS-CYS-SER-SER-LEU-LEU-PRO-ARG-ILE-HIS-CYS-ALA
hetero molecules


Theoretical massNumber of molelcules
Total (without water)73,0235
Polymers72,4422
Non-polymers5803
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2990 Å2
ΔGint-62 kcal/mol
Surface area24780 Å2
MethodPISA
Unit cell
Length a, b, c (Å)78.784, 75.958, 114.905
Angle α, β, γ (deg.)90.00, 102.15, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein / Protein/peptide , 2 types, 4 molecules ABCD

#1: Protein Processed angiotensin-converting enzyme 2


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 ALA-CYS-VAL-ARG-SER-HIS-CYS-SER-SER-LEU-LEU-PRO-ARG-ILE-HIS-CYS-ALA


Mass: 1855.241 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)

-
Non-polymers , 4 types, 133 molecules

#3: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: Zn
#4: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#5: Chemical ChemComp-LFI / 1-[3,5-bis(3-bromanylpropanoyl)-1,3,5-triazinan-1-yl]-3-bromanyl-propan-1-one / Chemical crosslinker


Mass: 492.002 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C12H18Br3N3O3 / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 128 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.32 Å3/Da / Density % sol: 46.99 %
Crystal growTemperature: 292 K / Method: vapor diffusion, hanging drop / Details: 0.2M (NH4)2H Cit, 20% w/v PEG 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Mar 11, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.07→77.02 Å / Num. obs: 72604 / % possible obs: 89.6 % / Redundancy: 5.9 % / CC1/2: 0.999 / Rmerge(I) obs: 0.078 / Rpim(I) all: 0.034 / Rrim(I) all: 0.085 / Net I/σ(I): 11.8 / Num. measured all: 426808
Reflection shellResolution: 2.07→2.1 Å / % possible obs: 49.8 % / Redundancy: 3.2 % / Rmerge(I) obs: 2.713 / Num. measured all: 6400 / Num. unique obs: 1998 / CC1/2: 0.349 / Rpim(I) all: 1.702 / Rrim(I) all: 3.223 / Net I/σ(I) obs: 0.1

-
Processing

Software
NameVersionClassification
REFMAC5.8.0352refinement
xia2data scaling
DIALSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.07→77.02 Å / Cor.coef. Fo:Fc: 0.966 / Cor.coef. Fo:Fc free: 0.932 / SU B: 22.504 / SU ML: 0.445 / Cross valid method: THROUGHOUT / ESU R: 0.319 / ESU R Free: 0.266 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.30363 3336 4.9 %RANDOM
Rwork0.22427 ---
obs0.22806 65401 84.82 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 75.69 Å2
Baniso -1Baniso -2Baniso -3
1-8.79 Å2-0 Å2-7.02 Å2
2---4 Å20 Å2
3----1.62 Å2
Refinement stepCycle: 1 / Resolution: 2.07→77.02 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9972 0 39 128 10139
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0060.01210307
X-RAY DIFFRACTIONr_bond_other_d0.0020.0169005
X-RAY DIFFRACTIONr_angle_refined_deg1.391.64713996
X-RAY DIFFRACTIONr_angle_other_deg0.4751.56121048
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.9951223
X-RAY DIFFRACTIONr_dihedral_angle_2_deg18.3325.65246
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.584101719
X-RAY DIFFRACTIONr_dihedral_angle_4_deg
X-RAY DIFFRACTIONr_chiral_restr0.0640.21461
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0211655
X-RAY DIFFRACTIONr_gen_planes_other0.0010.022093
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it5.9877.8614901
X-RAY DIFFRACTIONr_mcbond_other5.9877.8614901
X-RAY DIFFRACTIONr_mcangle_it9.07311.7686121
X-RAY DIFFRACTIONr_mcangle_other9.07311.7696122
X-RAY DIFFRACTIONr_scbond_it5.8017.9555406
X-RAY DIFFRACTIONr_scbond_other5.8017.9555407
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other8.51311.8327876
X-RAY DIFFRACTIONr_long_range_B_refined12.05898.01712285
X-RAY DIFFRACTIONr_long_range_B_other12.05898.01712285
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.07→2.123 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.747 47 -
Rwork0.691 1018 -
obs--17.92 %

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more