[English] 日本語
Yorodumi
- PDB-8rb6: Structure of Aldo-Keto Reductase 1C3 (AKR1C3) in complex with an ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8rb6
TitleStructure of Aldo-Keto Reductase 1C3 (AKR1C3) in complex with an inhibitor M689, with the 3-hydroxy-benzoisoxazole moiety. Resolution 2.0A
ComponentsAldo-keto reductase family 1 member C3
KeywordsOXIDOREDUCTASE / Aldo-keto reductase / AKR1C3 / inhibitor
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 / 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity / 3beta(or 20alpha)-hydroxysteroid dehydrogenase / 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 / 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity / 3beta(or 20alpha)-hydroxysteroid dehydrogenase / negative regulation of retinoic acid biosynthetic process / macromolecule metabolic process / 5alpha-androstane-3beta,17beta-diol dehydrogenase activity / Delta4-3-oxosteroid 5beta-reductase activity / 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+) / farnesol catabolic process / geranylgeranyl reductase activity / 3alpha-hydroxysteroid 3-dehydrogenase / : / cellular response to jasmonic acid stimulus / regulation of testosterone biosynthetic process / dihydrotestosterone 17-beta-dehydrogenase activity / androsterone dehydrogenase activity / testosterone biosynthetic process / 3alpha(or 20beta)-hydroxysteroid dehydrogenase / androstan-3-alpha,17-beta-diol dehydrogenase activity / testosterone dehydrogenase (NAD+) activity / 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 / Synthesis of Prostaglandins (PG) and Thromboxanes (TX) / estradiol 17-beta-dehydrogenase [NAD(P)+] activity / aldo-keto reductase (NADPH) activity / all-trans-retinol dehydrogenase (NAD+) activity / cyclooxygenase pathway / positive regulation of endothelial cell apoptotic process / prostaglandin H2 endoperoxidase reductase activity / all-trans-retinol dehydrogenase (NADP+) activity / Oxidoreductases; Acting on the CH-OH group of donors; With NAD+ or NADP+ as acceptor / oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor / daunorubicin metabolic process / doxorubicin metabolic process / bile acid binding / retinal dehydrogenase activity / 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 / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / Retinoid metabolism and transport / 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 / cytoplasm / cytosol
Similarity search - Function
Aldo-keto reductase family 1 member C / Aldo/keto reductase family putative active site signature. / Aldo/keto reductase family signature 1. / 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
Similarity search - Domain/homology
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 Å
AuthorsFrydenvang, K. / Mirza, O.A.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Eur.J.Med.Chem. / Year: 2024
Title: Structure-guided optimization of 3-hydroxybenzoisoxazole derivatives as inhibitors of Aldo-keto reductase 1C3 (AKR1C3) to target prostate cancer.
Authors: Pippione, A.C. / Kovachka, S. / Vigato, C. / Bertarini, L. / Mannella, I. / Sainas, S. / Rolando, B. / Denasio, E. / Piercy-Mycock, H. / Romalho, L. / Salladini, E. / Adinolfi, S. / Zonari, ...Authors: Pippione, A.C. / Kovachka, S. / Vigato, C. / Bertarini, L. / Mannella, I. / Sainas, S. / Rolando, B. / Denasio, E. / Piercy-Mycock, H. / Romalho, L. / Salladini, E. / Adinolfi, S. / Zonari, D. / Peraldo-Neia, C. / Chiorino, G. / Passoni, A. / Mirza, O.A. / Frydenvang, K. / Pors, K. / Lolli, M.L. / Spyrakis, F. / Oliaro-Bosso, S. / Boschi, D.
History
DepositionDec 3, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 6, 2024Provider: repository / Type: Initial release

-
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)76,0608
Polymers73,8122
Non-polymers2,2486
Water4,306239
1
A: Aldo-keto reductase family 1 member C3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,0304
Polymers36,9061
Non-polymers1,1243
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Aldo-keto reductase family 1 member C3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,0304
Polymers36,9061
Non-polymers1,1243
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)41.343, 93.191, 83.008
Angle α, β, γ (deg.)90.00, 95.09, 90.00
Int Tables number4
Space group name H-MP1211

-
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 / brain / 3-alpha- ...17-beta-hydroxysteroid dehydrogenase type 5 / 17-beta-HSD 5 / 3-alpha-HSD type II / brain / 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 / Prostaglandin F synthase / PGFS / Testosterone 17-beta-dehydrogenase 5


Mass: 36906.230 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 / Production host: Escherichia coli (E. coli)
References: UniProt: P42330, Oxidoreductases; Acting on the CH-OH group of donors; With NAD+ or NADP+ as acceptor, 3beta(or 20alpha)-hydroxysteroid dehydrogenase, 3alpha(or 20beta)-hydroxysteroid ...References: UniProt: P42330, Oxidoreductases; Acting on the CH-OH group of donors; With NAD+ or NADP+ as acceptor, 3beta(or 20alpha)-hydroxysteroid dehydrogenase, 3alpha(or 20beta)-hydroxysteroid dehydrogenase, 17beta-estradiol 17-dehydrogenase, 3alpha-hydroxysteroid 3-dehydrogenase, prostaglandin-F synthase, 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+), testosterone 17beta-dehydrogenase (NADP+)
#2: Chemical ChemComp-NAP / NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / 2'-MONOPHOSPHOADENOSINE 5'-DIPHOSPHORIBOSE


Mass: 743.405 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H28N7O17P3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-YMC / 4-[[4-(3-hydroxyphenyl)phenyl]amino]-1,2-benzoxazol-3-ol / 4-[(3'-hydroxy[1,1'-biphenyl]-4-yl)amino]-1,2-benzoxazol-3-ol


Mass: 318.326 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C19H14N2O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 239 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.16 Å3/Da / Density % sol: 43 %
Crystal growTemperature: 279 K / Method: vapor diffusion, hanging drop / pH: 6 / Details: 0.1 M MESH, 25% PEG3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: MAX IV / Beamline: BioMAX / Wavelength: 0.9762 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Sep 22, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9762 Å / Relative weight: 1
ReflectionResolution: 2→61.85 Å / Num. obs: 42384 / % possible obs: 100 % / Redundancy: 7 % / CC1/2: 0.997 / Rmerge(I) obs: 0.1 / Rpim(I) all: 0.041 / Rrim(I) all: 0.108 / Χ2: 0.92 / Net I/σ(I): 9 / Num. measured all: 296998
Reflection shellResolution: 2→2.05 Å / % possible obs: 100 % / Redundancy: 6.9 % / Rmerge(I) obs: 0.602 / Num. measured all: 21558 / Num. unique obs: 3131 / CC1/2: 0.944 / Rpim(I) all: 0.247 / Rrim(I) all: 0.652 / Χ2: 0.87 / Net I/σ(I) obs: 3

-
Processing

Software
NameVersionClassification
PHENIX(1.19.2_4158: ???)refinement
Aimlessdata scaling
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6f2u

6f2u


Resolution: 2→61.85 Å / SU ML: 0.21 / Cross valid method: THROUGHOUT / σ(F): 0.42 / Phase error: 26.81 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2266 2147 5.09 %
Rwork0.1899 --
obs0.1917 42198 99.57 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2→61.85 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4969 0 152 239 5360
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0035305
X-RAY DIFFRACTIONf_angle_d0.6037206
X-RAY DIFFRACTIONf_dihedral_angle_d13.5992049
X-RAY DIFFRACTIONf_chiral_restr0.044782
X-RAY DIFFRACTIONf_plane_restr0.004918
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2-2.050.31231480.24652674X-RAY DIFFRACTION100
2.05-2.10.27511330.22362642X-RAY DIFFRACTION100
2.1-2.150.26721430.21032692X-RAY DIFFRACTION100
2.15-2.220.24581510.20522625X-RAY DIFFRACTION100
2.22-2.290.24961580.22272660X-RAY DIFFRACTION99
2.29-2.370.25471490.20012650X-RAY DIFFRACTION100
2.37-2.470.26451380.2022656X-RAY DIFFRACTION100
2.47-2.580.23011480.2032686X-RAY DIFFRACTION100
2.58-2.710.23261620.19062613X-RAY DIFFRACTION99
2.71-2.880.20761520.18712652X-RAY DIFFRACTION100
2.88-3.110.22761380.19812699X-RAY DIFFRACTION100
3.11-3.420.24171240.18972699X-RAY DIFFRACTION100
3.42-3.910.19951350.18052675X-RAY DIFFRACTION100
3.91-4.930.18581180.15672708X-RAY DIFFRACTION99
4.93-61.850.22491500.19122720X-RAY DIFFRACTION99
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)
11.6705-0.40910.0911.62760.83530.4837-0.17590.0987-0.6252-0.02730.34070.06470.9594-0.19570.07450.8656-0.154-0.02640.2587-0.0510.3841-4.6908-33.612635.4902
22.79730.5799-0.11623.0740.75380.81140.10090.1833-0.6913-0.088-0.11750.38730.8811-0.32340.04780.8108-0.238-0.05440.434-0.08230.449-11.5042-34.166228.3149
33.05080.54790.19372.29610.10912.9328-0.02560.5179-0.0365-0.32880.01110.20940.065-0.29940.02410.45360.0116-0.07680.3604-0.00230.2203-5.4877-16.906125.0599
44.2908-1.4006-1.84833.23591.95994.90430.14940.57970.7799-0.6082-0.0541-0.2777-0.9871-0.147-0.02380.64280.0428-0.04370.35070.09780.29-1.2139-1.074522.7166
53.98110.09190.36452.8275-1.00164.14310.00940.10820.50440.0304-0.1150.3164-0.5303-0.59490.12820.42650.0987-0.05760.30650.00650.2495-7.112-4.515131.5933
60.2873-0.2083-0.33918.65523.65491.82220.26410.1855-0.16410.2038-0.5998-0.51650.42260.26560.3490.85790.0812-0.10860.69480.00520.38481.8442-21.707216.8918
71.9555-0.49640.81442.1957-0.53323.086-0.05690.20810.0651-0.40040.05380.0804-0.1414-0.1094-0.00330.2807-0.0234-0.04150.2035-0.01490.208-15.0044-18.101-18.674
83.4959-1.30931.47778.7452-6.88467.83-0.06590.304-0.5171-0.45970.17090.46920.1989-0.4101-0.25420.4413-0.0679-0.10220.2455-0.04840.3502-18.577-34.0465-18.5445
92.04610.22750.74624.3037-0.36655.1957-0.0109-0.0402-0.3047-0.27690.02350.22810.4186-0.2969-0.00050.2113-0.0175-0.03340.16520.01190.243-13.1606-32.2927-10.5419
104.8387-2.5314-0.00867.38521.07023.60130.2199-0.0462-0.81110.0869-0.0362-0.4130.8650.0637-0.20950.26940.0508-0.05280.26030.0150.3843-0.8367-34.1341-5.0539
114.6291-3.5013-0.24287.59321.78893.8054-0.0997-0.49620.1570.33750.108-0.46310.03990.2263-0.05470.2016-0.0102-0.03630.22780.01750.2342-2.8514-18.6001-0.2317
122.7851-2.42580.77027.06130.99323.8724-0.2275-0.5181-0.09680.04560.12640.2537-0.0775-0.35410.18170.1739-0.0209-0.04580.21410.01830.1744-13.5422-15.0207-3.3836
137.20232.7333-2.97544.984-4.23119.0806-0.2203-0.49330.81320.0601-0.19860.2231-0.5576-0.28160.35330.29730.0956-0.11690.2704-0.13540.3879-11.703-1.44611.0644
144.54740.50581.11894.03811.19173.4759-0.31510.27550.6695-0.3629-0.0226-0.0023-0.69780.09170.32470.3134-0.0301-0.06060.2010.0170.2523-9.0254-5.5154-10.8341
156.16441.53791.12025.31251.07564.0472-0.21030.04010.46060.15730.0214-0.8956-0.51040.79940.18150.3747-0.0865-0.12530.3147-0.02940.47011.4866-2.1579-1.184
160.06120.91110.04918.59550.29450.0497-0.0432-0.5854-0.08521.10550.18910.21980.0533-0.4314-0.18190.5357-0.0027-0.0150.65110.08320.3245-13.7301-22.59347.8143
173.0517-0.1170.27931.76290.38363.5864-0.075-0.0599-0.08030.271-0.0307-0.00090.15080.07090.09930.3756-0.0106-0.0470.18980.02170.18052.579-18.091242.058
182.9954-0.2630.4274.58630.14590.3345-0.0264-0.1731-0.38560.40270.0306-0.09380.86290.1586-0.00570.64090.0498-0.03620.25270.01470.27083.7445-30.427439.9301
194.07531.7687-1.16025.11770.88763.67480.05120.2082-0.7118-0.0364-0.041-0.5021.08670.6135-0.27690.95710.2066-0.0560.465-0.19890.446911.1323-35.205325.5198
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'B' and (resid 144 through 169 )
2X-RAY DIFFRACTION2chain 'B' and (resid 170 through 187 )
3X-RAY DIFFRACTION3chain 'B' and (resid 188 through 226 )
4X-RAY DIFFRACTION4chain 'B' and (resid 227 through 251 )
5X-RAY DIFFRACTION5chain 'B' and (resid 252 through 299 )
6X-RAY DIFFRACTION6chain 'B' and (resid 300 through 319 )
7X-RAY DIFFRACTION7chain 'A' and (resid 6 through 91 )
8X-RAY DIFFRACTION8chain 'A' and (resid 92 through 106 )
9X-RAY DIFFRACTION9chain 'A' and (resid 107 through 169 )
10X-RAY DIFFRACTION10chain 'A' and (resid 170 through 187 )
11X-RAY DIFFRACTION11chain 'A' and (resid 188 through 209 )
12X-RAY DIFFRACTION12chain 'A' and (resid 210 through 226 )
13X-RAY DIFFRACTION13chain 'A' and (resid 227 through 251 )
14X-RAY DIFFRACTION14chain 'A' and (resid 252 through 284 )
15X-RAY DIFFRACTION15chain 'A' and (resid 285 through 299 )
16X-RAY DIFFRACTION16chain 'A' and (resid 300 through 323 )
17X-RAY DIFFRACTION17chain 'B' and (resid 6 through 91 )
18X-RAY DIFFRACTION18chain 'B' and (resid 92 through 121 )
19X-RAY DIFFRACTION19chain 'B' and (resid 122 through 143 )

+
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://pdbjlvh1.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