[English] 日本語
Yorodumi
- PDB-4gja: Crystal structure of renin in complex with NVP-AYL747 (compound 5) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4gja
TitleCrystal structure of renin in complex with NVP-AYL747 (compound 5)
ComponentsRenin
KeywordsHYDROLASE/HYDROLASE INHIBITOR / renin inhibitor / fragment based screening / 3 / 5-disubstituted piperidines / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


Metabolism of Angiotensinogen to Angiotensins / response to cGMP / renin / renin-angiotensin regulation of aldosterone production / mesonephros development / drinking behavior / angiotensin maturation / regulation of MAPK cascade / response to cAMP / hormone-mediated signaling pathway ...Metabolism of Angiotensinogen to Angiotensins / response to cGMP / renin / renin-angiotensin regulation of aldosterone production / mesonephros development / drinking behavior / angiotensin maturation / regulation of MAPK cascade / response to cAMP / hormone-mediated signaling pathway / cell maturation / amyloid-beta metabolic process / insulin-like growth factor receptor binding / response to immobilization stress / cellular response to drug / regulation of blood pressure / male gonad development / kidney development / apical part of cell / peptidase activity / response to lipopolysaccharide / aspartic-type endopeptidase activity / proteolysis / signaling receptor binding / extracellular space / extracellular region / plasma membrane / cytoplasm
Renin-like domain / Peptidase family A1 domain / Aspartic peptidase A1 family / Aspartic peptidase, active site / Peptidase family A1 domain profile. / Aspartic peptidase, N-terminal / Eukaryotic and viral aspartyl proteases active site. / A1 Propeptide / Eukaryotic aspartyl protease / Aspartic peptidase domain superfamily
Renin
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.6 Å
AuthorsOstermann, N. / Zink, F. / Kroemer, M.
CitationJournal: J.Med.Chem. / Year: 2013
Title: A novel class of oral direct Renin inhibitors: highly potent 3,5-disubstituted piperidines bearing a tricyclic p3-p1 pharmacophore.
Authors: Ostermann, N. / Ruedisser, S. / Ehrhardt, C. / Breitenstein, W. / Marzinzik, A. / Jacoby, E. / Vangrevelinghe, E. / Ottl, J. / Klumpp, M. / Hartwieg, J.C. / Cumin, F. / Hassiepen, U. / Trappe, J. / Sedrani, R. / Geisse, S. / Gerhartz, B. / Richert, P. / Francotte, E. / Wagner, T. / Kromer, M. / Kosaka, T. / Webb, R.L. / Rigel, D.F. / Maibaum, J. / Baeschlin, D.K.
Validation Report
SummaryFull reportAbout validation report
History
DepositionAug 9, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 13, 2013Provider: repository / Type: Initial release
Revision 1.1Apr 10, 2013Group: Database references

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Renin
B: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)76,2209
Polymers74,5342
Non-polymers1,6867
Water3,873215
1
A: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,1585
Polymers37,2671
Non-polymers8914
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Renin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,0624
Polymers37,2671
Non-polymers7953
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
γ
α
β
Length a, b, c (Å)141.556, 141.556, 141.556
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number198
Space group name H-MP213

-
Components

#1: Protein/peptide 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 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P00797, renin
#2: Chemical ChemComp-NAG / N-ACETYL-D-GLUCOSAMINE


Mass: 221.208 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6 / N-Acetylglucosamine
#3: Chemical ChemComp-0M3 / (3S,5R)-N-(2,2-diphenylethyl)-5-{[(4-methylphenyl)sulfonyl]amino}piperidine-3-carboxamide


Mass: 477.618 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C27H31N3O3S
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4 / Sulfate
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 215 / Source method: isolated from a natural source / Formula: H2O / Water

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.17 Å3/Da / Density % sol: 61.22 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: reservoir: 18-21% PEG4000, 0.4-0.6 M sodium chloride, 50 mM sodium citrate, pH 4-5, protein solution: 10-15 mg/mL protein, 25 mM sodium chloride, 12.5 mM Tris, pH 8, drop: 1 uL protein solution + 1 uL reservoir, VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 95 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.979347 Å
DetectorType: MAR CCD 165 mm / Detector: CCD / Date: Apr 15, 2004
RadiationMonochromator: double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979347 Å / Relative weight: 1
ReflectionResolution: 2.6→50.05 Å / Num. obs: 29317 / % possible obs: 99.9 % / Observed criterion σ(F): 0 / Biso Wilson estimate: 71.32 Å2 / Rmerge(I) obs: 0.065 / Net I/σ(I): 21
Reflection shellResolution: 2.6→2.69 Å / Rmerge(I) obs: 0.407 / Mean I/σ(I) obs: 2.5 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
MOLREPphasing
BUSTER2.11.2refinement
DENZOdata reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: PDB ENTRY 2V0Z
Resolution: 2.6→50.05 Å / Cor.coef. Fo:Fc: 0.9493 / Cor.coef. Fo:Fc free: 0.9272 / SU R Cruickshank DPI: 0.422 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.432 / SU Rfree Blow DPI: 0.258 / SU Rfree Cruickshank DPI: 0.26 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.2304 2954 10.09 %RANDOM
Rwork0.1854 ---
Obs0.1899 29268 99.76 %-
Displacement parametersBiso mean: 60.61 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refine analyzeLuzzati coordinate error obs: 0.311 Å
Refinement stepCycle: LAST / Resolution: 2.6→50.05 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5196 0 111 215 5522
Refine LS restraints

Refinement-ID: X-RAY DIFFRACTION

TypeDev idealNumberRestraint functionWeight
t_bond_d0.015436HARMONIC2
t_angle_deg1.27384HARMONIC2
t_dihedral_angle_d1810SINUSOIDAL2
t_incorr_chiral_ct
t_pseud_angle
t_trig_c_planes112HARMONIC2
t_gen_planes794HARMONIC5
t_it5436HARMONIC20
t_nbd
t_omega_torsion3.54
t_other_torsion17.93
t_improper_torsion
t_chiral_improper_torsion722SEMIHARMONIC5
t_sum_occupancies
t_utility_distance
t_utility_angle
t_utility_torsion
t_ideal_dist_contact6219SEMIHARMONIC4
LS refinement shellResolution: 2.6→2.69 Å / Total num. of bins used: 15
RfactorNum. reflection% reflection
Rfree0.2942 292 10.41 %
Rwork0.2243 2513 -
All0.2314 2805 -
Obs-2805 99.76 %

+
About Yorodumi

-
News

-
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. (see PDBe EMDB page)
  • 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 at PDBe / 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. See below links for details.
  • 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

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.: Omokage search

+
Sep 15, 2016. EM Navigator & Yorodumi renewed

EM Navigator & Yorodumi renewed

  • New versions of EM Navigator and Yorodumi started

Related info.: Changes in new EM Navigator and Yorodumi

+
Aug 31, 2016. New EM Navigator & Yorodumi

New EM Navigator & Yorodumi

  • In 15th Sep 2016, the development versions of EM Navigator and Yorodumi will replace the official versions.
  • Current version will continue as 'legacy version' for some time.

Related info.: Changes in new EM Navigator and Yorodumi / EM Navigator / Yorodumi

Read more

-
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.

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