[English] 日本語
Yorodumi
- PDB-7jwu: Crystal structure of human ALDH1A1 bound to compound (R)-28 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7jwu
TitleCrystal structure of human ALDH1A1 bound to compound (R)-28
ComponentsRetinal dehydrogenase 1
KeywordsCYTOSOLIC PROTEIN / Rossmann fold
Function / homology
Function and homology information


fructosamine catabolic process / 3-deoxyglucosone dehydrogenase activity / benzaldehyde dehydrogenase (NAD+) / benzaldehyde dehydrogenase (NAD+) activity / maintenance of lens transparency / retinal dehydrogenase / gamma-aminobutyric acid biosynthetic process / aminobutyraldehyde dehydrogenase / aminobutyraldehyde dehydrogenase (NAD+) activity / Fructose catabolism ...fructosamine catabolic process / 3-deoxyglucosone dehydrogenase activity / benzaldehyde dehydrogenase (NAD+) / benzaldehyde dehydrogenase (NAD+) activity / maintenance of lens transparency / retinal dehydrogenase / gamma-aminobutyric acid biosynthetic process / aminobutyraldehyde dehydrogenase / aminobutyraldehyde dehydrogenase (NAD+) activity / Fructose catabolism / Ethanol oxidation / aldehyde metabolic process / RA biosynthesis pathway / glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity / aldehyde dehydrogenase (NAD+) / cellular detoxification of aldehyde / androgen binding / aldehyde dehydrogenase (NAD+) activity / retinal dehydrogenase activity / retinol metabolic process / negative regulation of cold-induced thermogenesis / retinoid metabolic process / GTPase activator activity / NAD binding / axon / synapse / extracellular exosome / cytosol / cytoplasm
Similarity search - Function
Aldehyde dehydrogenase, glutamic acid active site / Aldehyde dehydrogenases glutamic acid active site. / Aldehyde dehydrogenase, cysteine active site / Aldehyde dehydrogenases cysteine active site. / Aldehyde dehydrogenase domain / Aldehyde dehydrogenase family / Aldehyde dehydrogenase, C-terminal / Aldehyde dehydrogenase, N-terminal / Aldehyde/histidinol dehydrogenase
Similarity search - Domain/homology
NICOTINAMIDE-ADENINE-DINUCLEOTIDE / Chem-VMA / YTTERBIUM (III) ION / Aldehyde dehydrogenase 1A1 / Aldehyde dehydrogenase 1A1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsHurley, T.D. / Buchman, C.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01CA214567 United States
CitationJournal: Eur.J.Med.Chem. / Year: 2020
Title: Development of 2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one inhibitors of aldehyde dehydrogenase 1A (ALDH1A) as potential adjuncts to ovarian cancer chemotherapy.
Authors: Huddle, B.C. / Grimley, E. / Chtcherbinine, M. / Buchman, C.D. / Takahashi, C. / Debnath, B. / McGonigal, S.C. / Mao, S. / Li, S. / Felton, J. / Pan, S. / Wen, B. / Sun, D. / Neamati, N. / ...Authors: Huddle, B.C. / Grimley, E. / Chtcherbinine, M. / Buchman, C.D. / Takahashi, C. / Debnath, B. / McGonigal, S.C. / Mao, S. / Li, S. / Felton, J. / Pan, S. / Wen, B. / Sun, D. / Neamati, N. / Buckanovich, R.J. / Hurley, T.D. / Larsen, S.D.
History
DepositionAug 26, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 30, 2020Provider: repository / Type: Initial release
Revision 1.1Oct 18, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Retinal dehydrogenase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,3417
Polymers54,8981
Non-polymers1,4446
Water5,206289
1
A: Retinal dehydrogenase 1
hetero molecules

A: Retinal dehydrogenase 1
hetero molecules

A: Retinal dehydrogenase 1
hetero molecules

A: Retinal dehydrogenase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)225,36628
Polymers219,5904
Non-polymers5,77524
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_655-x+1,-y,z1
crystal symmetry operation5_655-x+1,y,-z1
crystal symmetry operation6_555x,-y,-z1
Buried area28230 Å2
ΔGint-232 kcal/mol
Surface area58050 Å2
MethodPISA
Unit cell
Length a, b, c (Å)109.032, 109.032, 82.888
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number89
Space group name H-MP422
Components on special symmetry positions
IDModelComponents
11A-979-

HOH

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Retinal dehydrogenase 1 / RalDH1 / ALDH-E1 / ALHDII / Aldehyde dehydrogenase family 1 member A1 / Aldehyde dehydrogenase / cytosolic


Mass: 54897.590 Da / Num. of mol.: 1 / Mutation: N121S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ALDH1A1, ALDC, ALDH1, PUMB1 / Plasmid: pET7b / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: V9HW83, UniProt: P00352*PLUS

-
Non-polymers , 5 types, 295 molecules

#2: Chemical ChemComp-YB / YTTERBIUM (III) ION


Mass: 173.040 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Yb
#3: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Cl
#4: Chemical ChemComp-NAD / NICOTINAMIDE-ADENINE-DINUCLEOTIDE


Mass: 663.425 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H27N7O14P2 / Comment: NAD*YM
#5: Chemical ChemComp-VMA / 1-methyl-5-phenyl-6-{[(1R)-1-(pyridin-2-yl)ethyl]sulfanyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one


Mass: 363.436 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H17N5OS / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 289 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.24 Å3/Da / Density % sol: 45.18 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.4
Details: 100 mM sodium BisTris, pH 6.4, 9% PEG3350, 200 mM NaCl, and 5-10 mM YbCl3, 250 uM 1-methyl-5-phenyl-6-((1-(pyridin-2-yl)ethyl)thio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one and 1% v/v DMSO

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-BM / Wavelength: 0.98 Å
DetectorType: ADSC QUANTUM 210r / Detector: CCD / Date: Mar 20, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.98 Å / Relative weight: 1
ReflectionResolution: 1.9→109.03 Å / Num. obs: 39319 / % possible obs: 98.4 % / Redundancy: 9.5 % / Rmerge(I) obs: 0.106 / Rpim(I) all: 0.036 / Rrim(I) all: 0.112 / Χ2: 1.052 / Net I/σ(I): 7.7
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
1.9-1.9390.77619150.9520.2670.8211.04797.5
1.93-1.979.20.69919140.9480.2390.741.04797.7
1.97-2.019.40.59519060.9660.2020.6291.06197.9
2.01-2.059.50.50419400.9750.170.5321.08298.2
2.05-2.099.50.45419270.9770.1530.481.0998.1
2.09-2.149.60.41119410.9820.1380.4331.09797.9
2.14-2.199.60.37518920.9820.1260.3961.10298.2
2.19-2.259.70.32519400.990.1090.3431.09898
2.25-2.329.70.2719590.9910.0910.2851.08698.3
2.32-2.399.70.24819330.9920.0830.2621.08498.6
2.39-2.489.60.24119810.9910.0810.2541.08499
2.48-2.589.70.19419520.9940.0650.2051.06798.7
2.58-2.79.60.15519590.9960.0520.1641.0698.8
2.7-2.849.60.13719800.9960.0460.1441.05699.3
2.84-3.029.60.10719800.9970.0360.1130.96199
3.02-3.259.50.08719920.9980.030.0920.97599.2
3.25-3.589.50.06920100.9980.0230.0730.96699.4
3.58-4.099.40.05620230.9990.0190.060.97899.6
4.09-5.169.20.04320610.9980.0150.0461.06699.2
5.16-508.60.05121140.9980.0180.0551.0496

-
Processing

Software
NameVersionClassification
HKL-2000data reduction
HKL-2000data scaling
REFMAC5.8.0155refinement
PDB_EXTRACT3.25data extraction
REFMACphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6DUM

6dum


Resolution: 1.9→109.03 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.935 / SU B: 13.127 / SU ML: 0.185 / SU R Cruickshank DPI: 0.1826 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.183 / ESU R Free: 0.173 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2625 1974 5.1 %RANDOM
Rwork0.2045 ---
obs0.2074 36888 97.23 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 74.65 Å2 / Biso mean: 40.803 Å2 / Biso min: 23.17 Å2
Baniso -1Baniso -2Baniso -3
1--2.31 Å20 Å20 Å2
2---2.31 Å20 Å2
3---4.62 Å2
Refinement stepCycle: final / Resolution: 1.9→109.03 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3814 0 74 289 4177
Biso mean--46.22 41.21 -
Num. residues----494
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0194003
X-RAY DIFFRACTIONr_bond_other_d0.0020.023804
X-RAY DIFFRACTIONr_angle_refined_deg1.3681.9835436
X-RAY DIFFRACTIONr_angle_other_deg0.90138786
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.2915501
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.99324.731167
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.34215677
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.1011517
X-RAY DIFFRACTIONr_chiral_restr0.0730.2598
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0214521
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02894
LS refinement shellResolution: 1.9→1.95 Å / Rfactor Rfree error: 0
RfactorNum. reflection% reflection
Rfree0.403 160 4.9 %
Rwork0.339 2670 -
obs--97.45 %
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)
11.32860.4297-0.43930.8741-0.39691.245-0.1252-0.141-0.09280.0944-0.04570.1430.1633-0.00540.17090.08160.0210.1090.03250.02690.528454.091-22.23221.091
20.79410.2726-0.32591.5122-0.96471.3048-0.1286-0.082-0.12050.1480.12130.26510.0125-0.19390.00730.05990.02350.08320.0822-0.01980.55628.213-10.31521.178
30.3248-0.4181-0.18780.7949-0.23360.9954-0.0631-0.02890.00120.1040.0042-0.0617-0.02690.06420.0590.0169-0.002-0.02820.01490.0420.459669.2113.144.893
400000000000000-00.17910.01550.1390.15990.13010.704430.408-29.68239.655
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A8 - 140
2X-RAY DIFFRACTION1A163 - 269
3X-RAY DIFFRACTION2A270 - 485
4X-RAY DIFFRACTION3A141 - 162
5X-RAY DIFFRACTION3A486 - 501
6X-RAY DIFFRACTION4A601

+
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