[English] 日本語
Yorodumi
- PDB-4q1n: Structure-based design of 4-hydroxy-3,5-substituted piperidines a... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4q1n
TitleStructure-based design of 4-hydroxy-3,5-substituted piperidines as direct renin inhibitors
ComponentsRenin
KeywordsHYDROLASE/HYDROLASE INHIBITOR / Aspartic protease / angiotensin / 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 / angiotensin maturation / Metabolism of Angiotensinogen to Angiotensins ...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 / angiotensin maturation / Metabolism of Angiotensinogen to Angiotensins / amyloid-beta metabolic process / 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
Chem-2Y9 / PHOSPHATE ION / Renin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.09 Å
AuthorsSchiering, N. / D'Arcy, A. / Irie, O. / Yokokawa, F.
CitationJournal: ACS Med Chem Lett / Year: 2014
Title: Structure-based design of substituted piperidines as a new class of highly efficacious oral direct Renin inhibitors.
Authors: Ehara, T. / Irie, O. / Kosaka, T. / Kanazawa, T. / Breitenstein, W. / Grosche, P. / Ostermann, N. / Suzuki, M. / Kawakami, S. / Konishi, K. / Hitomi, Y. / Toyao, A. / Gunji, H. / Cumin, F. / ...Authors: Ehara, T. / Irie, O. / Kosaka, T. / Kanazawa, T. / Breitenstein, W. / Grosche, P. / Ostermann, N. / Suzuki, M. / Kawakami, S. / Konishi, K. / Hitomi, Y. / Toyao, A. / Gunji, H. / Cumin, F. / Schiering, N. / Wagner, T. / Rigel, D.F. / Webb, R.L. / Maibaum, J. / Yokokawa, F.
History
DepositionApr 4, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 6, 2014Provider: repository / Type: Initial release
Revision 1.1Nov 22, 2017Group: Refinement description / Category: software / Item: _software.name
Revision 1.2Jul 29, 2020Group: Data collection / Derived calculations / Structure summary
Category: chem_comp / entity ...chem_comp / entity / pdbx_chem_comp_identifier / pdbx_entity_nonpoly / struct_conn / struct_site / struct_site_gen
Item: _chem_comp.name / _chem_comp.type ..._chem_comp.name / _chem_comp.type / _entity.pdbx_description / _pdbx_entity_nonpoly.name / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_role / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_label_asym_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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Renin
B: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)76,25510
Polymers74,5342
Non-polymers1,7218
Water7,476415
1
A: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,1365
Polymers37,2671
Non-polymers8694
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,1195
Polymers37,2671
Non-polymers8524
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
A: Renin
B: Renin
hetero molecules

A: Renin
B: Renin
hetero molecules

A: Renin
B: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)228,76530
Polymers223,6026
Non-polymers5,16324
Water1086
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation8_645-z+1,x-1/2,-y+1/21
crystal symmetry operation11_556y+1/2,-z+1/2,-x+11
Buried area17800 Å2
ΔGint-36 kcal/mol
Surface area72880 Å2
MethodPISA
Unit cell
Length a, b, c (Å)140.854, 140.854, 140.854
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number198
Space group name H-MP213

-
Components

-
Protein / Sugars , 2 types, 4 molecules AB

#1: Protein Renin / / Angiotensinogenase


Mass: 37267.008 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: REN / Cell line (production host): HEK / Production host: Homo Sapiens (human) / References: UniProt: P00797, renin
#3: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

-
Non-polymers , 4 types, 421 molecules

#2: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE / Dimethyl sulfoxide


Mass: 78.133 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-PO4 / PHOSPHATE ION / Phosphate


Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO4
#5: Chemical ChemComp-2Y9 / (3S,4R,5R)-N-cyclopropyl-N'-[(2R)-1-ethoxy-4-methylpentan-2-yl]-4-hydroxy-N-[5-(propan-2-yl)pyridin-2-yl]piperidine-3,5-dicarboxamide


Mass: 474.636 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C26H42N4O4
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 415 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.12 Å3/Da / Density % sol: 60.63 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 4.5
Details: 20% PEG 4000, 0.6 M NaCl, 0.05M sodium citrate, pH 4.5, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.9999 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Nov 20, 2008
RadiationMonochromator: double-crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9999 Å / Relative weight: 1
ReflectionResolution: 2.09→62.99 Å / Num. all: 55228 / Num. obs: 55186 / % possible obs: 99.9 % / Observed criterion σ(I): 3 / Biso Wilson estimate: 34.77 Å2 / Rsym value: 0.076 / Net I/σ(I): 16.7
Reflection shellResolution: 2.09→2.16 Å / Mean I/σ(I) obs: 3.7 / Rsym value: 0.52 / % possible all: 100

-
Processing

Software
NameVersionClassification
MAR345CCD SLSdata collection
PHASERphasing
BUSTER2.11.4refinement
XDSdata reduction
XSCALEdata scaling
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 2.09→62.99 Å / Cor.coef. Fo:Fc: 0.9546 / Cor.coef. Fo:Fc free: 0.9493 / SU R Cruickshank DPI: 0.149 / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.1888 2759 5 %RANDOM
Rwork0.1687 ---
all0.1697 55228 --
obs0.1697 55184 99.93 %-
Displacement parametersBiso mean: 39.42 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refine analyzeLuzzati coordinate error obs: 0.224 Å
Refinement stepCycle: LAST / Resolution: 2.09→62.99 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5184 0 113 415 5712
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0115469HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.167434HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1833SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes113HARMONIC2
X-RAY DIFFRACTIONt_gen_planes802HARMONIC5
X-RAY DIFFRACTIONt_it5469HARMONIC20
X-RAY DIFFRACTIONt_omega_torsion4.07
X-RAY DIFFRACTIONt_other_torsion17.22
X-RAY DIFFRACTIONt_chiral_improper_torsion732SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact6597SEMIHARMONIC4
LS refinement shellResolution: 2.09→2.14 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.1943 203 5.01 %
Rwork0.1879 3852 -
all0.1883 4055 -
obs--99.93 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.65940.2926-0.4380.6197-0.46871.1896-0.09080.0724-0.0153-0.14920.02950.03330.1361-0.09130.0612-0.0210.0017-0.0394-0.0815-0.0129-0.034766.594711.612641.0916
21.31970.15460.13961.1266-0.24550.9512-0.09240.1229-0.0731-0.18130.0003-0.14830.05620.07920.0921-0.02120.03070.0254-0.0999-0.0041-0.097783.126235.044517.3247
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|* }A-5 - 709
2X-RAY DIFFRACTION2{ B|* }B-5 - 706

+
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