[English] 日本語
Yorodumi
- PDB-4dbu: Crystal structure of human 17beta-hydroxysteroid dehydrogenase ty... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4dbu
TitleCrystal structure of human 17beta-hydroxysteroid dehydrogenase type 5 (AKR1C3) in complex with NADP+ and 3-((4 -(trifluoromethyl)phenyl)amino)benzoic acid
ComponentsAldo-keto reductase family 1 member C3
KeywordsOXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / castrate resistant prostate cancer / AKR1C3 selective inhibitor / TIM Barrel / steroid metabolism / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex
Function / homology
Function and homology information


prostaglandin-F synthase / testosterone 17beta-dehydrogenase (NADP+) / prostaglandin D2 11-ketoreductase activity / ketoreductase activity / prostaglandin-F synthase activity / cellular response to prostaglandin stimulus / cellular response to corticosteroid stimulus / 3beta(or 20alpha)-hydroxysteroid dehydrogenase / 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity / negative regulation of retinoic acid biosynthetic process ...prostaglandin-F synthase / testosterone 17beta-dehydrogenase (NADP+) / prostaglandin D2 11-ketoreductase activity / ketoreductase activity / prostaglandin-F synthase activity / cellular response to prostaglandin stimulus / cellular response to corticosteroid stimulus / 3beta(or 20alpha)-hydroxysteroid dehydrogenase / 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity / negative regulation of retinoic acid biosynthetic process / 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+) / 5alpha-androstane-3beta,17beta-diol dehydrogenase activity / delta4-3-oxosteroid 5beta-reductase activity / farnesol catabolic process / geranylgeranyl reductase activity / 3alpha-hydroxysteroid 3-dehydrogenase / phenanthrene 9,10-monooxygenase activity / macromolecule metabolic process / regulation of testosterone biosynthetic process / cellular response to jasmonic acid stimulus / 3alpha(or 20beta)-hydroxysteroid dehydrogenase / androstan-3-alpha,17-beta-diol dehydrogenase activity / dihydrotestosterone 17-beta-dehydrogenase activity / androsterone dehydrogenase activity / testosterone dehydrogenase (NAD+) activity / testosterone biosynthetic process / RA biosynthesis pathway / regulation of retinoic acid receptor signaling pathway / cellular response to prostaglandin D stimulus / ketosteroid monooxygenase activity / Synthesis of bile acids and bile salts via 24-hydroxycholesterol / retinal metabolic process / testosterone 17-beta-dehydrogenase (NADP+) activity / progesterone metabolic process / 17beta-estradiol 17-dehydrogenase / estradiol 17-beta-dehydrogenase [NAD(P)] activity / Synthesis of Prostaglandins (PG) and Thromboxanes (TX) / aldo-keto reductase (NADPH) activity / cyclooxygenase pathway / all-trans-retinol dehydrogenase (NAD+) activity / prostaglandin H2 endoperoxidase reductase activity / positive regulation of endothelial cell apoptotic process / all-trans-retinol dehydrogenase (NADP+) activity / Oxidoreductases; Acting on the CH-OH group of donors; With NAD+ or NADP+ as acceptor / daunorubicin metabolic process / doxorubicin metabolic process / oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor / retinal dehydrogenase activity / bile acid binding / aldose reductase (NADPH) activity / retinoid metabolic process / prostaglandin metabolic process / renal absorption / steroid metabolic process / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Retinoid metabolism and transport / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / keratinocyte differentiation / cellular response to calcium ion / cellular response to starvation / response to nutrient / male gonad development / positive regulation of reactive oxygen species metabolic process / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / G protein-coupled receptor signaling pathway / positive regulation of cell population proliferation / extracellular exosome / nucleus / cytosol / cytoplasm
Similarity search - Function
Aldo-keto reductase family 1 member C / Aldo/keto reductase family putative active site signature. / Aldo/keto reductase family signature 1. / NADP-dependent oxidoreductase domain / Aldo/keto reductase family signature 2. / Aldo/keto reductase, conserved site / Aldo-keto reductase / NADP-dependent oxidoreductase domain / Aldo/keto reductase family / NADP-dependent oxidoreductase domain superfamily ...Aldo-keto reductase family 1 member C / Aldo/keto reductase family putative active site signature. / Aldo/keto reductase family signature 1. / NADP-dependent oxidoreductase domain / Aldo/keto reductase family signature 2. / Aldo/keto reductase, conserved site / Aldo-keto reductase / NADP-dependent oxidoreductase domain / Aldo/keto reductase family / NADP-dependent oxidoreductase domain superfamily / TIM Barrel / Alpha-Beta Barrel / Alpha Beta
Similarity search - Domain/homology
3-{[4-(trifluoromethyl)phenyl]amino}benzoic acid / NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Aldo-keto reductase family 1 member C3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.528 Å
AuthorsChen, M. / Christianson, D.W. / Winkler, J.D. / Penning, T.M.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2012
Title: Crystal structures of AKR1C3 containing an N-(aryl)amino-benzoate inhibitor and a bifunctional AKR1C3 inhibitor and androgen receptor antagonist. Therapeutic leads for castrate resistant prostate cancer.
Authors: Chen, M. / Adeniji, A.O. / Twenter, B.M. / Winkler, J.D. / Christianson, D.W. / Penning, T.M.
History
DepositionJan 16, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 28, 2012Provider: repository / Type: Initial release
Revision 1.1Apr 11, 2012Group: Other
Revision 1.2May 2, 2012Group: Database references
Revision 1.3May 23, 2012Group: Database references
Revision 1.4Nov 15, 2017Group: Refinement description / Category: software
Item: _software.classification / _software.contact_author ..._software.classification / _software.contact_author / _software.contact_author_email / _software.date / _software.language / _software.location / _software.name / _software.type / _software.version
Revision 1.5Sep 13, 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_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _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: Aldo-keto reductase family 1 member C3
B: Aldo-keto reductase family 1 member C3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)75,8426
Polymers73,7922
Non-polymers2,0494
Water2,936163
1
A: Aldo-keto reductase family 1 member C3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,9213
Polymers36,8961
Non-polymers1,0252
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Aldo-keto reductase family 1 member C3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,9213
Polymers36,8961
Non-polymers1,0252
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)47.268, 49.136, 84.725
Angle α, β, γ (deg.)71.900, 81.580, 70.260
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein Aldo-keto reductase family 1 member C3 / 17-beta-hydroxysteroid dehydrogenase type 5 / 17-beta-HSD 5 / 3-alpha-HSD type II / 3-alpha- ...17-beta-hydroxysteroid dehydrogenase type 5 / 17-beta-HSD 5 / 3-alpha-HSD type II / 3-alpha-hydroxysteroid dehydrogenase type 2 / 3-alpha-HSD type 2 / Chlordecone reductase homolog HAKRb / Dihydrodiol dehydrogenase 3 / DD-3 / DD3 / Dihydrodiol dehydrogenase type I / HA1753 / Indanol dehydrogenase / Prostaglandin F synthase / PGFS / Testosterone 17-beta-dehydrogenase 5 / Trans-1 / 2-dihydrobenzene-1 / 2-diol dehydrogenase


Mass: 36896.215 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: AKR1C3, DDH1, HSD17B5, KIAA0119, PGFS / Plasmid: PET16B / Production host: Escherichia coli (E. coli) / Strain (production host): C41(DE3)
References: UniProt: P42330, EC: 1.1.1.213, indanol dehydrogenase, prostaglandin-F synthase, EC: 1.1.1.63, testosterone 17beta-dehydrogenase (NADP+), trans-1,2-dihydrobenzene-1,2-diol 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-BT9 / 3-{[4-(trifluoromethyl)phenyl]amino}benzoic acid


Mass: 281.230 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H10F3NO2
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 163 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsH5Q IS A NATURAL VARIANT.

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.38 Å3/Da / Density % sol: 48.39 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 15% PEG8000, 0.1 M MES, pH 6.0, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: NSLS / Beamline: X29A / Wavelength: 0.9795 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Nov 22, 2010
RadiationMonochromator: sagitally focused Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.528→50 Å / Num. all: 22648 / Num. obs: 22331 / % possible obs: 98.6 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 2.2 % / Biso Wilson estimate: 37.3 Å2 / Rmerge(I) obs: 0.093 / Χ2: 1.019 / Net I/σ(I): 6.7
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
2.528-2.622.10.31522421.035197.9
2.62-2.732.20.26322121.022197.8
2.73-2.852.20.21222041.014198.4
2.85-32.20.16922361.024198.4
3-3.192.20.14122141.015198.4
3.19-3.432.20.10822360.966198.5
3.43-3.782.20.07522561.013198.8
3.78-4.332.20.06522381.011199
4.33-5.452.10.05922451.044199.2
5.45-502.20.05122481.045199.4

-
Processing

Software
NameVersionClassificationNB
DENZOdata reduction
SCALEPACKdata scaling
PHENIX1.5_2refinement
PDB_EXTRACT3.1data extraction
HKL-2000data collection
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1S2A

1s2a


Resolution: 2.528→44.505 Å / Occupancy max: 1 / Occupancy min: 1 / FOM work R set: 0.7411 / SU ML: 0.42 / Isotropic thermal model: ISOTROPIC / Cross valid method: THROUGHOUT / σ(F): 0.1 / Phase error: 32.62 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2939 1027 4.88 %RANDOM
Rwork0.2277 ---
all0.253 22331 --
obs0.231 21058 92.32 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 20.813 Å2 / ksol: 0.309 e/Å3
Displacement parametersBiso max: 104.07 Å2 / Biso mean: 29.0633 Å2 / Biso min: 10.15 Å2
Baniso -1Baniso -2Baniso -3
1-14.9303 Å2-3.4691 Å25.3177 Å2
2---6.2206 Å20.0399 Å2
3----8.7097 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.46 Å0.34 Å
Luzzati d res low-50 Å
Luzzati sigma a0.51 Å0.38 Å
Refinement stepCycle: LAST / Resolution: 2.528→44.505 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5078 0 136 163 5377
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0035341
X-RAY DIFFRACTIONf_angle_d0.6317251
X-RAY DIFFRACTIONf_chiral_restr0.045783
X-RAY DIFFRACTIONf_plane_restr0.003925
X-RAY DIFFRACTIONf_dihedral_angle_d18.7542085
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 7

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.528-2.66140.38621270.2812534266181
2.6614-2.82810.33971370.26742715285287
2.8281-3.04640.35291520.25132749290190
3.0464-3.35290.32391490.24382937308694
3.3529-3.83780.2951520.21653017316998
3.8378-4.83430.23221700.19113001317198
4.8343-44.51220.24471400.20453078321899

+
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