[English] 日本語
Yorodumi
- PDB-8b66: Human Aldose Reductase Mutant A299G in Complex with a Ligand with... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8b66
TitleHuman Aldose Reductase Mutant A299G in Complex with a Ligand with an IDD Structure (3-({[2-(carboxymethoxy)-4-fluorobenzoyl]amino}methyl)benzoic acid)
ComponentsAldo-keto reductase family 1 member B1
KeywordsOXIDOREDUCTASE / human Aldose Reductase / hAR / Aldo-keto-reductase / SAR_061 ligand / nadp+ / diabetes / mutant A299G / closed transient pocket
Function / homology
Function and homology information


glyceraldehyde oxidoreductase activity / Fructose biosynthesis / fructose biosynthetic process / L-glucuronate reductase activity / aldose reductase / D/L-glyceraldehyde reductase / glycerol dehydrogenase (NADP+) activity / C21-steroid hormone biosynthetic process / NADP-retinol dehydrogenase / Pregnenolone biosynthesis ...glyceraldehyde oxidoreductase activity / Fructose biosynthesis / fructose biosynthetic process / L-glucuronate reductase activity / aldose reductase / D/L-glyceraldehyde reductase / glycerol dehydrogenase (NADP+) activity / C21-steroid hormone biosynthetic process / NADP-retinol dehydrogenase / Pregnenolone biosynthesis / allyl-alcohol dehydrogenase / allyl-alcohol dehydrogenase activity / prostaglandin H2 endoperoxidase reductase activity / regulation of urine volume / all-trans-retinol dehydrogenase (NADP+) activity / metanephric collecting duct development / daunorubicin metabolic process / doxorubicin metabolic process / retinal dehydrogenase (NAD+) activity / aldose reductase (NADPH) activity / epithelial cell maturation / cellular hyperosmotic salinity response / retinoid metabolic process / renal water homeostasis / carbohydrate metabolic process / electron transfer activity / negative regulation of apoptotic process / mitochondrion / extracellular space / extracellular exosome / nucleoplasm / cytosol
Similarity search - Function
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
Chem-4G7 / CITRIC ACID / NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Aldo-keto reductase family 1 member B1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 0.95 Å
AuthorsHubert, L.-S. / Heine, A. / Klebe, G.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: To Be Published
Title: Human Aldose Reductase Mutant A299G in Complex with a Ligand with an IDD Structure (3-({[2-(carboxymethoxy)-4-fluorobenzoyl]amino}methyl)benzoic acid)
Authors: Hubert, L.-S. / Heine, A. / Klebe, G.
History
DepositionSep 26, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 11, 2023Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Aldo-keto reductase family 1 member B1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,3924
Polymers36,1101
Non-polymers1,2833
Water8,485471
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1500 Å2
ΔGint-5 kcal/mol
Surface area13200 Å2
MethodPISA
Unit cell
Length a, b, c (Å)47.374, 66.881, 49.361
Angle α, β, γ (deg.)90.000, 91.935, 90.000
Int Tables number4
Space group name H-MP1211
Space group name HallP2yb
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z

-
Components

#1: Protein Aldo-keto reductase family 1 member B1 / Aldehyde reductase / Aldose reductase / AR


Mass: 36109.543 Da / Num. of mol.: 1 / Mutation: A299G
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: AKR1B1, ALDR1, ALR2 / Plasmid: pET15b / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P15121, NADP-retinol dehydrogenase, D/L-glyceraldehyde reductase, allyl-alcohol dehydrogenase, aldose reductase
#2: Chemical ChemComp-NAP / NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / 2'-MONOPHOSPHOADENOSINE 5'-DIPHOSPHORIBOSE


Mass: 743.405 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H28N7O17P3
#3: Chemical ChemComp-CIT / CITRIC ACID


Mass: 192.124 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H8O7
#4: Chemical ChemComp-4G7 / 3-({[2-(carboxymethoxy)-4-fluorobenzoyl]amino}methyl)benzoic acid


Mass: 347.295 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H14FNO6 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 471 / 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: 43.17 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 5
Details: 50 mM Di-Ammoniumhydrogen citrate pH 5: 15 mg/mL hAR, 5.2 mg/mL DTT, 0.7 mg/mL NADP+, 5% (w/v) PEG 6000; Reservoir: 120 mM Di-Ammoniumhydrogen citrate pH 5, 20% (w/v) PEG 6000; Soaking- ...Details: 50 mM Di-Ammoniumhydrogen citrate pH 5: 15 mg/mL hAR, 5.2 mg/mL DTT, 0.7 mg/mL NADP+, 5% (w/v) PEG 6000; Reservoir: 120 mM Di-Ammoniumhydrogen citrate pH 5, 20% (w/v) PEG 6000; Soaking-conditions: 120 mM di-ammonium hydrogen citrate pH 5.0, 25% PEG 6000, saturated with inhibitor

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.2 / Wavelength: 0.9184 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 1, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9184 Å / Relative weight: 1
ReflectionResolution: 0.95→49.3 Å / Num. obs: 187062 / % possible obs: 96.9 % / Redundancy: 5.7 % / Biso Wilson estimate: 6.34 Å2 / CC1/2: 0.997 / Rsym value: 0.059 / Net I/σ(I): 18.9
Reflection shellResolution: 0.95→1.01 Å / Redundancy: 4.8 % / Mean I/σ(I) obs: 6.84 / Num. unique obs: 26689 / CC1/2: 0.97 / Rsym value: 0.17 / % possible all: 85.6

-
Processing

Software
NameVersionClassification
PHENIX1.18.2_3874refinement
Cootmodel building
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4PRR

4prr


Resolution: 0.95→39.7 Å / SU ML: 0.0617 / Cross valid method: FREE R-VALUE / σ(F): 1.4 / Phase error: 8.3421
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.1154 3742 2 %
Rwork0.1052 183310 -
obs0.1054 187052 96.87 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 10.29 Å2
Refinement stepCycle: LAST / Resolution: 0.95→39.7 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2512 0 83 471 3066
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00652990
X-RAY DIFFRACTIONf_angle_d1.06814109
X-RAY DIFFRACTIONf_chiral_restr0.0826447
X-RAY DIFFRACTIONf_plane_restr0.0083573
X-RAY DIFFRACTIONf_dihedral_angle_d16.22111160
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
0.95-0.960.1374970.13414753X-RAY DIFFRACTION68.3
0.96-0.970.14631120.12175478X-RAY DIFFRACTION78.28
0.97-0.990.11131310.11156397X-RAY DIFFRACTION91.07
0.99-10.12281410.1056899X-RAY DIFFRACTION99.51
1-1.020.10161410.09866924X-RAY DIFFRACTION99.45
1.02-1.030.11081420.09476979X-RAY DIFFRACTION99.29
1.03-1.050.10591420.0896934X-RAY DIFFRACTION98.97
1.05-1.070.09111390.08526812X-RAY DIFFRACTION97.9
1.07-1.090.09971390.08316828X-RAY DIFFRACTION97.85
1.09-1.110.08631430.0816976X-RAY DIFFRACTION99.64
1.11-1.130.08511410.08066905X-RAY DIFFRACTION99.53
1.13-1.160.09511440.0827059X-RAY DIFFRACTION99.56
1.16-1.180.10821410.08336909X-RAY DIFFRACTION98.99
1.18-1.210.09151390.08426835X-RAY DIFFRACTION97.77
1.21-1.240.10231410.08526883X-RAY DIFFRACTION98.35
1.24-1.280.09331420.0896991X-RAY DIFFRACTION99.66
1.28-1.320.11531420.09256971X-RAY DIFFRACTION99.69
1.32-1.370.10441430.09376960X-RAY DIFFRACTION99.48
1.37-1.420.10621410.09496931X-RAY DIFFRACTION98.94
1.42-1.490.09931390.09466832X-RAY DIFFRACTION97.22
1.49-1.570.0991430.09587006X-RAY DIFFRACTION99.86
1.57-1.670.0871430.0976998X-RAY DIFFRACTION99.92
1.67-1.790.10341430.10626991X-RAY DIFFRACTION99.66
1.79-1.980.13321430.11327002X-RAY DIFFRACTION98.95
1.98-2.260.12141410.11296939X-RAY DIFFRACTION98.76
2.26-2.850.11451440.1247028X-RAY DIFFRACTION99.58
2.85-39.70.1561450.12997090X-RAY DIFFRACTION99.04

+
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