[English] 日本語
Yorodumi
- PDB-5sy2: Structure-based design of a new series of N-piperidin-3-ylpyrimid... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5sy2
TitleStructure-based design of a new series of N-piperidin-3-ylpyrimidine-5-carboxamides as renin inhibitors
ComponentsRenin
KeywordsHYDROLASE/HYDROLASE INHIBITOR / protein-ligand complex / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


renin / mesonephros development / juxtaglomerular apparatus development / response to cGMP / renin-angiotensin regulation of aldosterone production / drinking behavior / regulation of MAPK cascade / response to immobilization stress / amyloid-beta metabolic process / Metabolism of Angiotensinogen to Angiotensins ...renin / mesonephros development / juxtaglomerular apparatus development / response to cGMP / renin-angiotensin regulation of aldosterone production / drinking behavior / regulation of MAPK cascade / response to immobilization stress / amyloid-beta metabolic process / Metabolism of Angiotensinogen to Angiotensins / cell maturation / angiotensin maturation / response to cAMP / insulin-like growth factor receptor binding / hormone-mediated signaling pathway / kidney development / regulation of blood pressure / male gonad development / apical part of cell / cellular response to xenobiotic stimulus / 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-74V / TRIETHYLENE GLYCOL / Renin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.25 Å
AuthorsSnell, G.P. / Behnke, C.A. / Okada, K. / Hideyuki, O. / Sang, B.C. / Lane, W.
CitationJournal: Bioorg.Med.Chem. / Year: 2016
Title: Structure-based design of a new series of N-(piperidin-3-yl)pyrimidine-5-carboxamides as renin inhibitors.
Authors: Imaeda, Y. / Tawada, M. / Suzuki, S. / Tomimoto, M. / Kondo, M. / Tarui, N. / Sanada, T. / Kanagawa, R. / Snell, G. / Behnke, C.A. / Kubo, K. / Kuroita, T.
History
DepositionAug 10, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 2, 2016Provider: repository / Type: Initial release
Revision 1.1Nov 9, 2016Group: Database references
Revision 1.2Jul 29, 2020Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp / citation ...chem_comp / citation / entity / pdbx_chem_comp_identifier / pdbx_entity_nonpoly / pdbx_struct_oper_list / struct_conn / struct_site / struct_site_gen
Item: _chem_comp.name / _chem_comp.type ..._chem_comp.name / _chem_comp.type / _citation.journal_id_CSD / _entity.pdbx_description / _pdbx_entity_nonpoly.name / _pdbx_struct_oper_list.symmetry_operation / _struct_conn.pdbx_role
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 1.3Oct 23, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature
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)76,20810
Polymers74,5342
Non-polymers1,6748
Water4,936274
1
A: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,1386
Polymers37,2671
Non-polymers8715
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,0704
Polymers37,2671
Non-polymers8033
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)228,62430
Polymers223,6026
Non-polymers5,02224
Water1086
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation5_555z,x,y1
crystal symmetry operation9_555y,z,x1
Buried area19060 Å2
ΔGint-15 kcal/mol
Surface area73150 Å2
MethodPISA
Unit cell
Length a, b, c (Å)137.540, 137.540, 137.540
Angle α, β, γ (deg.)90.000, 90.000, 90.000
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): HEK293 / 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: 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 , 5 types, 280 molecules

#3: Chemical ChemComp-74V / N-ethyl-4-{[(furan-2-yl)methyl]amino}-2-methyl-N-[(3S)-piperidin-3-yl]pyrimidine-5-carboxamide


Mass: 343.423 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C18H25N5O2
#4: Chemical ChemComp-PGE / TRIETHYLENE GLYCOL


Mass: 150.173 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H14O4
#5: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#6: Chemical ChemComp-1PE / PENTAETHYLENE GLYCOL / PEG400


Mass: 238.278 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H22O6 / Comment: precipitant*YM
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 274 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.92 Å3/Da / Density % sol: 57.86 % / Mosaicity: 0.509 °
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.9 / Details: 23% PEG600, 0.06M citrate, 0.04M citric acid

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 4r / Detector: CCD / Date: Aug 31, 2006
RadiationMonochromator: Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.25→50.01 Å / Num. obs: 41044 / % possible obs: 99.6 % / Redundancy: 5.9 % / Rmerge(I) obs: 0.081 / Net I/av σ(I): 18.319 / Net I/σ(I): 9.9
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsDiffraction-ID% possible all
2.25-2.324.80.508198.6
2.32-2.395.20.426199.1
2.39-2.485.30.377199.1
2.48-2.585.50.306199.1
2.58-2.695.70.237199.4
2.69-2.835.90.183199.6
2.83-3.016.20.136199.9
3.01-3.246.40.1051100
3.24-3.576.50.0731100
3.57-4.096.40.0561100
4.09-5.156.40.0481100
5.15-506.20.038199.8

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
HKL-2000data collection
HKL-2000data scaling
HKL-2000data reduction
REFMAC5.8.0135refinement
PDB_EXTRACT3.2data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.25→50.01 Å / Cor.coef. Fo:Fc: 0.951 / Cor.coef. Fo:Fc free: 0.934 / SU B: 10.873 / SU ML: 0.138 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.24 / ESU R Free: 0.19 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.221 2061 5 %RANDOM
Rwork0.1847 ---
obs0.1866 38946 99.54 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 71.53 Å2 / Biso mean: 35.424 Å2 / Biso min: 19.1 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refinement stepCycle: final / Resolution: 2.25→50.01 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5071 0 112 274 5457
Biso mean--44.25 37.29 -
Num. residues----665
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0195325
X-RAY DIFFRACTIONr_bond_other_d0.0020.024857
X-RAY DIFFRACTIONr_angle_refined_deg1.3391.9677214
X-RAY DIFFRACTIONr_angle_other_deg0.901311196
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.2045663
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.13824.178213
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.92615822
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.0541517
X-RAY DIFFRACTIONr_chiral_restr0.0770.2813
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.025941
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021202
X-RAY DIFFRACTIONr_mcbond_it0.7162.3582658
X-RAY DIFFRACTIONr_mcbond_other0.7142.3582657
X-RAY DIFFRACTIONr_mcangle_it1.2783.5283313
LS refinement shellResolution: 2.253→2.311 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.271 155 -
Rwork0.237 2831 -
all-2986 -
obs--98.55 %
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)
11.50581.27650.41732.68530.47110.6037-0.14070.13470.0715-0.19510.1519-0.0402-0.14250.0564-0.01120.04750.00520.00610.06240.010.011830.219763.260444.1096
21.3881-0.42940.13411.4165-0.64192.1328-0.0511-0.02220.14450.05060.0486-0.1036-0.07350.10580.00260.0219-0.01130.02120.0158-0.02170.059946.67486.613767.4582
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A2 - 78
2X-RAY DIFFRACTION1A79 - 91
3X-RAY DIFFRACTION1A92 - 154
4X-RAY DIFFRACTION1A155 - 248
5X-RAY DIFFRACTION1A249 - 265
6X-RAY DIFFRACTION1A266 - 280
7X-RAY DIFFRACTION1A281 - 298
8X-RAY DIFFRACTION1A299 - 302
9X-RAY DIFFRACTION1A303 - 312
10X-RAY DIFFRACTION1A313 - 340
11X-RAY DIFFRACTION2B1 - 78
12X-RAY DIFFRACTION2B79 - 91
13X-RAY DIFFRACTION2B92 - 154
14X-RAY DIFFRACTION2B155 - 248
15X-RAY DIFFRACTION2B249 - 265
16X-RAY DIFFRACTION2B266 - 280
17X-RAY DIFFRACTION2B281 - 298
18X-RAY DIFFRACTION2B299 - 302
19X-RAY DIFFRACTION2B303 - 312
20X-RAY DIFFRACTION2B313 - 340

+
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