[English] 日本語
Yorodumi
- PDB-3q5h: Clinically Useful Alkyl Amine Renin Inhibitors -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3q5h
TitleClinically Useful Alkyl Amine Renin Inhibitors
ComponentsRenin
KeywordsHYDROLASE/HYDROLASE INHIBITOR / aspartate protease / hypertension / renin expression / renin inhibitor / aspartyl protease / cleavage on pair of basic residues / disease mutation / glycoprotein / membrane / protease / secreted / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


renin / juxtaglomerular apparatus development / mesonephros development / response to cGMP / renin-angiotensin regulation of aldosterone production / drinking behavior / regulation of MAPK cascade / response to immobilization stress / amyloid-beta metabolic process / angiotensin maturation ...renin / juxtaglomerular apparatus development / mesonephros development / response to cGMP / renin-angiotensin regulation of aldosterone production / drinking behavior / regulation of MAPK cascade / response to immobilization stress / amyloid-beta metabolic process / angiotensin maturation / Metabolism of Angiotensinogen to Angiotensins / cell maturation / response to cAMP / insulin-like growth factor receptor binding / hormone-mediated signaling pathway / kidney development / regulation of blood pressure / male gonad development / cellular response to xenobiotic stimulus / apical part of cell / peptidase activity / response to lipopolysaccharide / aspartic-type endopeptidase activity / signaling receptor binding / proteolysis / extracellular space / extracellular region / plasma membrane
Similarity search - Function
Renin-like domain / Aspartic peptidase, N-terminal / A1 Propeptide / Eukaryotic aspartyl protease / Aspartic peptidase A1 family / Peptidase family A1 domain / Peptidase family A1 domain profile. / Cathepsin D, subunit A; domain 1 / Acid Proteases / Aspartic peptidase, active site ...Renin-like domain / Aspartic peptidase, N-terminal / A1 Propeptide / Eukaryotic aspartyl protease / Aspartic peptidase A1 family / Peptidase family A1 domain / Peptidase family A1 domain profile. / Cathepsin D, subunit A; domain 1 / Acid Proteases / Aspartic peptidase, active site / Eukaryotic and viral aspartyl proteases active site. / Aspartic peptidase domain superfamily / Beta Barrel / Mainly Beta
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.16 Å
AuthorsWu, Z. / McKeever, B.M.
CitationJournal: ACS Med Chem Lett / Year: 2011
Title: Discovery of VTP-27999, an Alkyl Amine Renin Inhibitor with Potential for Clinical Utility.
Authors: Jia, L. / Simpson, R.D. / Yuan, J. / Xu, Z. / Zhao, W. / Cacatian, S. / Tice, C.M. / Guo, J. / Ishchenko, A. / Singh, S.B. / Wu, Z. / McKeever, B.M. / Bukhtiyarov, Y. / Johnson, J.A. / Doe, ...Authors: Jia, L. / Simpson, R.D. / Yuan, J. / Xu, Z. / Zhao, W. / Cacatian, S. / Tice, C.M. / Guo, J. / Ishchenko, A. / Singh, S.B. / Wu, Z. / McKeever, B.M. / Bukhtiyarov, Y. / Johnson, J.A. / Doe, C.P. / Harrison, R.K. / McGeehan, G.M. / Dillard, L.W. / Baldwin, J.J. / Claremon, D.A.
History
DepositionDec 28, 2010Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 30, 2011Provider: repository / Type: Initial release
Revision 1.1Sep 24, 2014Group: Database references
Revision 1.2Jul 17, 2019Group: Data collection / Derived calculations / Refinement description
Category: software / struct_conn
Item: _software.classification / _software.name ..._software.classification / _software.name / _software.version / _struct_conn.pdbx_leaving_atom_flag
Revision 2.0Jul 29, 2020Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Derived calculations / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / pdbx_validate_close_contact / struct_asym / struct_conn / struct_site / struct_site_gen
Item: _atom_site.auth_asym_id / _atom_site.auth_seq_id ..._atom_site.auth_asym_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _chem_comp.name / _chem_comp.type / _entity.formula_weight / _entity.pdbx_description / _entity.pdbx_number_of_molecules / _entity.type / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_validate_close_contact.auth_asym_id_1 / _pdbx_validate_close_contact.auth_seq_id_1 / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_role / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 2.1Sep 13, 2023Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 2.2Nov 6, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Renin
B: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)76,22111
Polymers74,5342
Non-polymers1,6879
Water3,027168
1
A: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,3587
Polymers37,2671
Non-polymers1,0916
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,8634
Polymers37,2671
Non-polymers5963
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)54.650, 97.850, 149.006
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Renin / Angiotensinogenase


Mass: 37267.008 Da / Num. of mol.: 2 / Fragment: UNP residues 67-406
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: REN, renin / Plasmid: pcDNA3.1 / Cell line (production host): HEK 293 / Production host: Homo sapiens (human) / References: UniProt: P00797, renin
#2: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}LINUCSPDB-CARE
#3: Chemical
ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: Cl
#4: Chemical ChemComp-RX6 / methyl (2-{(R)-(3-chlorophenyl)[(3R)-1-({(2S)-1-(methylamino)-3-[(3R)-tetrahydro-2H-pyran-3-yl]propan-2-yl}carbamoyl)piperidin-3-yl]methoxy}ethyl)carbamate


Mass: 525.081 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C26H41ClN4O5
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 168 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.67 Å3/Da / Density % sol: 53.98 %
Crystal growTemperature: 278 K / Method: vapor diffusion, hanging drop
Details: 0.1 M Tris-HCl, 0.2 M ammonium sulfate, 18-26% PEG3550, 5 mg/mL renin, 1 mm inhibitor, pH 7.0-8.0, VAPOR DIFFUSION, HANGING DROP, temperature 278K
PH range: 7.0-8.0

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: NSLS / Beamline: X8C / Wavelength: 1.1
DetectorType: ADSC QUANTUM 4r / Detector: CCD / Date: Aug 4, 2006
RadiationMonochromator: Si (111) Double-crystal monochromator / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.1 Å / Relative weight: 1
ReflectionResolution: 2.16→48.93 Å / Num. all: 43723 / Num. obs: 41821 / % possible obs: 95.6 % / Redundancy: 5 % / Rmerge(I) obs: 0.086 / Net I/σ(I): 18.31

-
Processing

Software
NameVersionClassification
REFMAC5.5.0102refinement
CNSrefinement
CBASSdata collection
HKL-2000data reduction
HKL-2000data scaling
CNSphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3GW5

3gw5


Resolution: 2.16→48.92 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.928 / SU B: 7.626 / SU ML: 0.188 / Cross valid method: THROUGHOUT / ESU R: 0.279 / ESU R Free: 0.223 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.26839 2099 5 %RANDOM
Rwork0.2239 ---
obs0.22619 39698 95.76 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 42.456 Å2
Baniso -1Baniso -2Baniso -3
1--0.03 Å20 Å20 Å2
2--0.01 Å20 Å2
3---0.02 Å2
Refinement stepCycle: LAST / Resolution: 2.16→48.92 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5204 0 106 168 5478
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.020.0225469
X-RAY DIFFRACTIONr_angle_refined_deg1.9531.9827419
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.9665669
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.04924.196224
X-RAY DIFFRACTIONr_dihedral_angle_3_deg18.88715864
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.4331520
X-RAY DIFFRACTIONr_chiral_restr0.1290.2839
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.0214079
X-RAY DIFFRACTIONr_mcbond_it1.0991.53329
X-RAY DIFFRACTIONr_mcangle_it2.01925376
X-RAY DIFFRACTIONr_scbond_it3.00232140
X-RAY DIFFRACTIONr_scangle_it4.784.52043
LS refinement shellResolution: 2.161→2.217 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.47 106 -
Rwork0.356 2179 -
obs--72.13 %

+
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