[English] 日本語
Yorodumi
- PDB-4bb5: Free-Wilson and Structural Approaches to Co-optimising Human and ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4bb5
TitleFree-Wilson and Structural Approaches to Co-optimising Human and Rodent Isoform Potency for 11b-Hydroxysteroid Dehydrogenase Type 1 11b-HSD1 Inhibitors
ComponentsCORTICOSTEROID 11-BETA-DEHYDROGENASE ISOZYME 1
KeywordsOXIDOREDUCTASE
Function / homology
Function and homology information


11-beta-hydroxysteroid dehydrogenase (NADP+) activity / 11beta-hydroxysteroid dehydrogenase / cortisol dehydrogenase activity / 7beta-hydroxysteroid dehydrogenase (NADP+) / 7-beta-hydroxysteroid dehydrogenase (NADP+) activity / Glucocorticoid biosynthesis / steroid catabolic process / Prednisone ADME / steroid binding / lung development ...11-beta-hydroxysteroid dehydrogenase (NADP+) activity / 11beta-hydroxysteroid dehydrogenase / cortisol dehydrogenase activity / 7beta-hydroxysteroid dehydrogenase (NADP+) / 7-beta-hydroxysteroid dehydrogenase (NADP+) activity / Glucocorticoid biosynthesis / steroid catabolic process / Prednisone ADME / steroid binding / lung development / NADP binding / intracellular membrane-bounded organelle / endoplasmic reticulum membrane / protein homodimerization activity / membrane
Similarity search - Function
: / short chain dehydrogenase / Short-chain dehydrogenase/reductase, conserved site / Short-chain dehydrogenases/reductases family signature. / Short-chain dehydrogenase/reductase SDR / NAD(P)-binding Rossmann-like Domain / NAD(P)-binding domain superfamily / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-HD2 / NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / 11-beta-hydroxysteroid dehydrogenase 1
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsGoldberg, F.W. / Leach, A.G. / Scott, J.S. / Snelson, W.L. / Groombridge, S.D. / Donald, C.S. / Bennett, S.N.L. / Bodin, C. / Morentin Gutierrez, P. / Gyte, A.C.
CitationJournal: J.Med.Chem. / Year: 2012
Title: Free-Wilson and Structural Approaches to Co-Optimising Human and Rodent Isoform Potency for 11Beta-Hydroxysteroid Dehydrogenase Type 1 (11Beta-Hsd1) Inhibitors
Authors: Goldberg, F.W. / Leach, A.G. / Scott, J.S. / Snelson, W.L. / Groombridge, S.D. / Donald, C.S. / Bennett, S.N.L. / Bodin, C. / Morentin Gutierrez, P. / Gyte, A.C.
History
DepositionSep 20, 2012Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 28, 2012Provider: repository / Type: Initial release
Revision 1.1Dec 26, 2012Group: Database references / Refinement description
Revision 1.2May 8, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: CORTICOSTEROID 11-BETA-DEHYDROGENASE ISOZYME 1
B: CORTICOSTEROID 11-BETA-DEHYDROGENASE ISOZYME 1
C: CORTICOSTEROID 11-BETA-DEHYDROGENASE ISOZYME 1
D: CORTICOSTEROID 11-BETA-DEHYDROGENASE ISOZYME 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)134,40312
Polymers129,7234
Non-polymers4,6808
Water5,621312
1
A: CORTICOSTEROID 11-BETA-DEHYDROGENASE ISOZYME 1
B: CORTICOSTEROID 11-BETA-DEHYDROGENASE ISOZYME 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,2026
Polymers64,8622
Non-polymers2,3404
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area8460 Å2
ΔGint-56.2 kcal/mol
Surface area20140 Å2
MethodPISA
2
C: CORTICOSTEROID 11-BETA-DEHYDROGENASE ISOZYME 1
D: CORTICOSTEROID 11-BETA-DEHYDROGENASE ISOZYME 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,2026
Polymers64,8622
Non-polymers2,3404
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7660 Å2
ΔGint-49.2 kcal/mol
Surface area19800 Å2
MethodPISA
Unit cell
Length a, b, c (Å)48.781, 132.482, 154.819
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121
Noncrystallographic symmetry (NCS)NCS oper:
IDCodeMatrixVector
1given(-0.661, -0.042, 0.75), (-0.044, -0.995, -0.095), (0.75, -0.096, 0.655)45.85834, -8.10008, -21.26853
2given(1, 0.022, -0.013), (0.02, -0.989, -0.149), (-0.016, 0.148, -0.989)-17.43429, -2.66651, -98.71673
3given(-0.663, -0.083, 0.744), (-0.069, 0.996, 0.05), (-0.745, -0.018, -0.667)28.60017, 10.33007, -79.23773

-
Components

#1: Protein
CORTICOSTEROID 11-BETA-DEHYDROGENASE ISOZYME 1 / 11B-HYDROXYSTEROID DEHYDROGENASE TYPE 1 / BHSD / 11-BETA-HYDROXYSTEROID DEHYDROGENASE 1 / 11-DH / 11-BETA-HSD1


Mass: 32430.818 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli)
References: UniProt: P28845, 11beta-hydroxysteroid dehydrogenase
#2: Chemical
ChemComp-NAP / NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / 2'-MONOPHOSPHOADENOSINE 5'-DIPHOSPHORIBOSE


Mass: 743.405 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C21H28N7O17P3
#3: Chemical
ChemComp-HD2 / 4-cyclopentyl-N-[(1S,3R)-5-oxidanyl-2-adamantyl]-2-[[(3S)-oxolan-3-yl]amino]pyrimidine-5-carboxamide


Mass: 426.552 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C24H34N4O3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 312 / 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: 2.2 Å3/Da / Density % sol: 44 % / Description: NONE
Crystal growpH: 7 / Details: pH 7

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 1.072
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Nov 10, 2011
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.072 Å / Relative weight: 1
ReflectionResolution: 2.1→48.09 Å / Num. obs: 59410 / % possible obs: 99.6 % / Observed criterion σ(I): 1 / Redundancy: 6.8 % / Biso Wilson estimate: 23.89 Å2 / Rmerge(I) obs: 0.16 / Net I/σ(I): 10.2
Reflection shellResolution: 2.1→2.15 Å / Redundancy: 3.2 % / Rmerge(I) obs: 0.76 / Mean I/σ(I) obs: 3.2 / % possible all: 98.7

-
Processing

Software
NameVersionClassification
BUSTER2.11.1refinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.2→35 Å / Cor.coef. Fo:Fc: 0.9313 / Cor.coef. Fo:Fc free: 0.9034 / SU R Cruickshank DPI: 0.284 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.294 / SU Rfree Blow DPI: 0.198 / SU Rfree Cruickshank DPI: 0.198
Details: NUMBER OF LIBRARIES USED: 9 REFINEMENT NOTE 1: IDEAL-DIST CONTACT TERM CONTACT SETUP ALL ATOMS HAVE CCP4 ATOM TYPE FROM LIBRARY. NCS REPRESENTATION: RESTRAINT LSSR (- AUTONCS)
RfactorNum. reflection% reflectionSelection details
Rfree0.2204 2607 5.04 %RANDOM
Rwork0.1825 ---
obs0.1843 51750 99.64 %-
Displacement parametersBiso mean: 25.57 Å2
Baniso -1Baniso -2Baniso -3
1--2.7998 Å20 Å20 Å2
2--0.206 Å20 Å2
3---2.5937 Å2
Refine analyzeLuzzati coordinate error obs: 0.242 Å
Refinement stepCycle: LAST / Resolution: 2.2→35 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8013 0 316 312 8641
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.018496HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.1511524HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d2903SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes185HARMONIC2
X-RAY DIFFRACTIONt_gen_planes1269HARMONIC5
X-RAY DIFFRACTIONt_it8496HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.25
X-RAY DIFFRACTIONt_other_torsion18.09
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion1134SEMIHARMONIC5
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_contact10490SEMIHARMONIC4
LS refinement shellResolution: 2.2→2.26 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.243 165 4.43 %
Rwork0.2295 3559 -
all0.2302 3724 -
obs--99.64 %

+
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