[English] 日本語
Yorodumi
- PDB-4hfr: Human 11beta-Hydroxysteroid Dehydrogenase Type 1 in complex with ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4hfr
TitleHuman 11beta-Hydroxysteroid Dehydrogenase Type 1 in complex with an orally bioavailable acidic inhibitor AZD4017.
ComponentsCorticosteroid 11-beta-dehydrogenase isozyme 1
KeywordsOxidoreductase/Oxidoreductase inhibitor / Alpha Beta / Rossmann fold / NADP / Oxidoreductase-Oxidoreductase inhibitor complex
Function / homology
Function and homology information


11beta-hydroxysteroid dehydrogenase / 11-beta-hydroxysteroid dehydrogenase (NADP+) activity / cortisol dehydrogenase activity / 7beta-hydroxysteroid dehydrogenase (NADP+) / 7-beta-hydroxysteroid dehydrogenase (NADP+) activity / Glucocorticoid biosynthesis / steroid catabolic process / Prednisone ADME / steroid binding / lung development ...11beta-hydroxysteroid dehydrogenase / 11-beta-hydroxysteroid dehydrogenase (NADP+) activity / 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-14M / NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / 11-beta-hydroxysteroid dehydrogenase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.73 Å
AuthorsOgg, D.J. / Gerhardt, S. / Hargreaves, D.
CitationJournal: J.Med.Chem. / Year: 2012
Title: Discovery of a Potent, Selective, and Orally Bioavailable Acidic 11 -Hydroxysteroid Dehydrogenase Type 1 (11 -HSD1) Inhibitor: Discovery of 2-[(3S)-1-[5-(Cyclohexylcarbamoyl)-6- ...Title: Discovery of a Potent, Selective, and Orally Bioavailable Acidic 11 -Hydroxysteroid Dehydrogenase Type 1 (11 -HSD1) Inhibitor: Discovery of 2-[(3S)-1-[5-(Cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic Acid (AZD4017)
Authors: Scott, J.S. / Bowker, S.S. / Deschoolmeester, J. / Gerhardt, S. / Hargreaves, D. / Kilgour, E. / Lloyd, A. / Mayers, R.M. / McCoull, W. / Newcombe, N.J. / Ogg, D. / Packer, M.J. / Rees, A. / ...Authors: Scott, J.S. / Bowker, S.S. / Deschoolmeester, J. / Gerhardt, S. / Hargreaves, D. / Kilgour, E. / Lloyd, A. / Mayers, R.M. / McCoull, W. / Newcombe, N.J. / Ogg, D. / Packer, M.J. / Rees, A. / Revill, J. / Schofield, P. / Selmi, N. / Swales, J.G. / Whittamore, P.R.
History
DepositionOct 5, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 17, 2012Provider: repository / Type: Initial release
Revision 1.1Nov 12, 2014Group: Structure summary
Revision 1.2Jan 24, 2018Group: Structure summary / Category: audit_author / Item: _audit_author.name
Revision 1.3Sep 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)62,0756
Polymers59,7492
Non-polymers2,3264
Water724
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7160 Å2
ΔGint-54 kcal/mol
Surface area20070 Å2
MethodPISA
2
A: Corticosteroid 11-beta-dehydrogenase isozyme 1
B: Corticosteroid 11-beta-dehydrogenase isozyme 1
hetero molecules

A: Corticosteroid 11-beta-dehydrogenase isozyme 1
B: Corticosteroid 11-beta-dehydrogenase isozyme 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)124,15012
Polymers119,4984
Non-polymers4,6528
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation6_555-x,-x+y,-z+1/31
Buried area16610 Å2
ΔGint-128 kcal/mol
Surface area37840 Å2
MethodPISA
Unit cell
Length a, b, c (Å)108.193, 108.193, 135.290
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number152
Space group name H-MP3121

-
Components

#1: Protein Corticosteroid 11-beta-dehydrogenase isozyme 1 / 11-beta-hydroxysteroid dehydrogenase 1 / 11-DH / 11-beta-HSD1


Mass: 29874.564 Da / Num. of mol.: 2 / Mutation: M179L, L262R, C272S, F278E,
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HSD11B1, HSD11, HSD11L / 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 / Nicotinamide adenine dinucleotide phosphate


Mass: 743.405 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H28N7O17P3
#3: Chemical ChemComp-14M / {(3S)-1-[5-(cyclohexylcarbamoyl)-6-(propylsulfanyl)pyridin-2-yl]piperidin-3-yl}acetic acid


Mass: 419.581 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H33N3O3S
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 4 / 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: 3.83 Å3/Da / Density % sol: 67.85 %
Crystal growMethod: vapor diffusion / pH: 8.5
Details: 42% PEG400, 100 mM Tris-HCl, pH 8.5, VAPOR DIFFUSION

-
Data collection

Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.93 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Oct 30, 2006
RadiationMonochromator: High resolution Si(311) cut and a lower resolution Si(111) cut
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.93 Å / Relative weight: 1
ReflectionResolution: 2.73→54.5 Å / Num. all: 24156 / Num. obs: 24156 / % possible obs: 97.6 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Redundancy: 3.6 % / Biso Wilson estimate: 97.96 Å2 / Rmerge(I) obs: 0.056 / Net I/σ(I): 13.5
Reflection shellResolution: 2.73→2.8 Å / Redundancy: 3.7 % / Rmerge(I) obs: 0.57 / % possible all: 99.1

-
Processing

Software
NameVersionClassification
ADSCQuantumdata collection
AMoREphasing
BUSTER2.11.2refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2BEL

2bel


Resolution: 2.73→21.32 Å / Cor.coef. Fo:Fc: 0.9257 / Cor.coef. Fo:Fc free: 0.9202 / SU R Cruickshank DPI: 0.394 / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.2265 1226 5.11 %RANDOM
Rwork0.199 ---
obs0.2004 24014 96.85 %-
Displacement parametersBiso mean: 100.95 Å2
Baniso -1Baniso -2Baniso -3
1--10.9 Å20 Å20 Å2
2---10.9 Å20 Å2
3---21.7999 Å2
Refine analyzeLuzzati coordinate error obs: 0.507 Å
Refinement stepCycle: LAST / Resolution: 2.73→21.32 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3895 0 154 4 4053
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.014122HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.255579HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1460SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes76HARMONIC2
X-RAY DIFFRACTIONt_gen_planes641HARMONIC5
X-RAY DIFFRACTIONt_it4122HARMONIC20
X-RAY DIFFRACTIONt_omega_torsion2.85
X-RAY DIFFRACTIONt_other_torsion20.24
X-RAY DIFFRACTIONt_chiral_improper_torsion549SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact4794SEMIHARMONIC4
LS refinement shellResolution: 2.73→2.85 Å / Total num. of bins used: 12
RfactorNum. reflection% reflection
Rfree0.2402 157 5.3 %
Rwork0.2223 2807 -
all0.2232 2964 -
obs--96.85 %
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)
11.65990.12740.56782.4623-0.80685.5728-0.0976-0.06010.31380.05230.19670.088-1.70350.4026-0.09910.0996-0.3890.0706-0.1953-0.0357-0.2764-12.233466.642724.5387
22.00150.14861.03571.3503-0.55514.51040.2588-0.0699-0.50370.11110.0684-0.18590.57111.1173-0.3272-0.3681-0.0595-0.08890.1939-0.0687-0.1603-1.67739.951335.4028
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|26 - A|285 }A26 - 285
2X-RAY DIFFRACTION2{ B|26 - B|283 }B26 - 283

+
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