[English] 日本語
Yorodumi
- PDB-4xx3: Renin in complex with (S)-1-(3-(benzylcarbamoyl)benzyl)-4-isoprop... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4xx3
TitleRenin in complex with (S)-1-(3-(benzylcarbamoyl)benzyl)-4-isopropyl-4-methyl-6-oxotetrahydropyrimidin-2(1H)-iminium
ComponentsRenin
KeywordsHydrolase/Hydrolase Inhibitor / Animals / Antihypertensive Agents / Blood Pressure / Drug Design / Enzyme Inhibitors / Models / Molecular / Protein Conformation / Rats / Renin / Structure-Activity Relationship / 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 / amyloid-beta metabolic process ...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 / amyloid-beta metabolic process / Metabolism of Angiotensinogen to Angiotensins / cell maturation / response to cAMP / hormone-mediated signaling pathway / kidney development / insulin-like growth factor receptor binding / 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 / MOLECULAR REPLACEMENT / Resolution: 2.4 Å
AuthorsOrth, P.
CitationJournal: Bioorg. Med. Chem. Lett. / Year: 2015
Title: Iminopyrimidinones: a novel pharmacophore for the development of orally active renin inhibitors.
Authors: McKittrick, B.A. / Caldwell, J.P. / Bara, T. / Boykow, G. / Chintala, M. / Clader, J. / Czarniecki, M. / Courneya, B. / Duffy, R. / Fleming, L. / Giessert, R. / Greenlee, W.J. / Heap, C. / ...Authors: McKittrick, B.A. / Caldwell, J.P. / Bara, T. / Boykow, G. / Chintala, M. / Clader, J. / Czarniecki, M. / Courneya, B. / Duffy, R. / Fleming, L. / Giessert, R. / Greenlee, W.J. / Heap, C. / Hong, L. / Huang, Y. / Iserloh, U. / Josien, H. / Khan, T. / Korfmacher, W. / Liang, X. / Mazzola, R. / Mitra, S. / Moore, K. / Orth, P. / Rajagopalan, M. / Roy, S. / Sakwa, S. / Strickland, C. / Vaccaro, H. / Voigt, J. / Wang, H. / Wong, J. / Zhang, R. / Zych, A.
History
DepositionJan 29, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 18, 2015Provider: repository / Type: Initial release
Revision 1.1Mar 16, 2016Group: Data collection
Revision 1.2Nov 22, 2017Group: Derived calculations / Refinement description / Category: pdbx_struct_oper_list / software / Item: _pdbx_struct_oper_list.symmetry_operation
Revision 1.3Apr 18, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_abbrev / _citation.journal_volume ..._citation.journal_abbrev / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.4Jul 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_role
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 1.5Sep 27, 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Renin
B: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)75,7616
Polymers74,5342
Non-polymers1,2274
Water4,990277
1
A: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,8813
Polymers37,2671
Non-polymers6142
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,8813
Polymers37,2671
Non-polymers6142
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)227,28418
Polymers223,6026
Non-polymers3,68212
Water1086
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation5_555z,x,y1
crystal symmetry operation9_555y,z,x1
Buried area14850 Å2
ΔGint-44 kcal/mol
Surface area72910 Å2
MethodPISA
4
A: Renin
hetero molecules

A: Renin
hetero molecules

A: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)113,6429
Polymers111,8013
Non-polymers1,8416
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation5_555z,x,y1
crystal symmetry operation9_555y,z,x1
Buried area3960 Å2
ΔGint-19 kcal/mol
Surface area40370 Å2
MethodPISA
5
B: Renin
hetero molecules

B: Renin
hetero molecules

B: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)113,6429
Polymers111,8013
Non-polymers1,8416
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation5_555z,x,y1
crystal symmetry operation9_555y,z,x1
Buried area4660 Å2
ΔGint-22 kcal/mol
Surface area38780 Å2
MethodPISA
Unit cell
Length a, b, c (Å)142.020, 142.020, 142.020
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number198
Space group name H-MP213
Components on special symmetry positions
IDModelComponents
11A-623-

HOH

-
Components

#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): 293 HEK / Production host: Homo sapiens (human) / References: UniProt: P00797, renin
#2: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 2 / Source method: obtained synthetically / 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
#3: Chemical ChemComp-70X / N-benzyl-3-{[(2Z,4S)-2-imino-4-methyl-6-oxo-4-(propan-2-yl)tetrahydropyrimidin-1(2H)-yl]methyl}benzamide


Mass: 392.494 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H28N4O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 277 / 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: 3.22 Å3/Da / Density % sol: 61.86 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop
Details: Reservoir 15% PEG3350, 625 mM NaCl and citrate buffer pH 4.6

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E DW / Wavelength: 1.54178 Å
DetectorType: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: May 27, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54178 Å / Relative weight: 1
ReflectionResolution: 2.4→50 Å / Num. obs: 36678 / % possible obs: 97.4 % / Redundancy: 3.4 % / Rmerge(I) obs: 0.1 / Χ2: 1.069 / Net I/av σ(I): 8.982 / Net I/σ(I): 11.1 / Num. measured all: 123848
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible allMean I/σ(I) obs
2.4-2.492.90.70133981.081191.3
2.49-2.5930.55935081.08793.9
2.59-2.73.10.42935731.12295.8
2.7-2.853.20.31336281.08997.3
2.85-3.023.30.22636841.03798.2
3.02-3.263.40.16636931.09699.1
3.26-3.583.60.11937481.09799.7
3.58-4.13.70.08837751.07599.9
4.1-5.173.70.06637861.01699.910
5.17-503.70.04738851.02298.610

-
Processing

Software
NameVersionClassification
BUSTER-TNTBUSTER 2.11.4refinement
DENZOdata reduction
SCALEPACKdata scaling
PDB_EXTRACT3.1data extraction
AMoREphasing
BUSTER2.11.4refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 2I4Q

2i4q


Resolution: 2.4→47.34 Å / Cor.coef. Fo:Fc: 0.9403 / Cor.coef. Fo:Fc free: 0.9359 / Occupancy max: 1 / Occupancy min: 0.5 / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.2243 1406 3.84 %RANDOM
Rwork0.2071 ---
obs0.2078 36595 97.45 %-
Displacement parametersBiso max: 128.7 Å2 / Biso mean: 45.9629 Å2 / Biso min: 20.06 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refine analyzeLuzzati coordinate error obs: 0.332 Å
Refinement stepCycle: LAST / Resolution: 2.4→47.34 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5116 0 86 277 5479
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1730SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes108HARMONIC2
X-RAY DIFFRACTIONt_gen_planes807HARMONIC5
X-RAY DIFFRACTIONt_it5332HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion722SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact6127SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d5332HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg7267HARMONIC21.18
X-RAY DIFFRACTIONt_omega_torsion3.67
X-RAY DIFFRACTIONt_other_torsion17.84
LS refinement shellResolution: 2.4→2.47 Å / Total num. of bins used: 18
RfactorNum. reflection% reflection
Rfree0.2273 110 3.9 %
Rwork0.2396 2708 -
all0.2391 2818 -
obs--97.45 %

+
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://pdbjlvh1.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