[English] 日本語
Yorodumi
- PDB-4kak: Crystal structure of human dihydrofolate reductase complexed with... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4kak
TitleCrystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3S)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)
ComponentsDihydrofolate reductase
KeywordsOxidoreductase/oxidoreductase inhibitor / Oxidoreductase / 5 / 6 / 7 / 8-tetrahydrofolate / NADP+ / 8-dihydrofolate / Hydride shift / Oxidoreductase-oxidoreductase inhibitor complex
Function / homology
Function and homology information


regulation of removal of superoxide radicals / tetrahydrobiopterin biosynthetic process / Metabolism of folate and pterines / tetrahydrofolate metabolic process / response to methotrexate / sequence-specific mRNA binding / axon regeneration / folic acid binding / dihydrofolate metabolic process / G1/S-Specific Transcription ...regulation of removal of superoxide radicals / tetrahydrobiopterin biosynthetic process / Metabolism of folate and pterines / tetrahydrofolate metabolic process / response to methotrexate / sequence-specific mRNA binding / axon regeneration / folic acid binding / dihydrofolate metabolic process / G1/S-Specific Transcription / dihydrofolate reductase / dihydrofolate reductase activity / folic acid metabolic process / NADPH binding / tetrahydrofolate biosynthetic process / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / one-carbon metabolic process / positive regulation of nitric-oxide synthase activity / mRNA regulatory element binding translation repressor activity / NADP binding / negative regulation of translation / mRNA binding / mitochondrion / cytosol
Similarity search - Function
Dihydrofolate reductase / Dihydrofolate Reductase, subunit A / Dihydrofolate Reductase, subunit A / Dihydrofolate reductase conserved site / Dihydrofolate reductase (DHFR) domain signature. / Dihydrofolate reductase (DHFR) domain profile. / Dihydrofolate reductase domain / Dihydrofolate reductase / Dihydrofolate reductase-like domain superfamily / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-06U / ETHANOL / Chem-NDP / Dihydrofolate reductase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.8 Å
AuthorsLamb, K.M. / Anderson, A.C.
CitationJournal: Biochemistry / Year: 2013
Title: Elucidating features that drive the design of selective antifolates using crystal structures of human dihydrofolate reductase.
Authors: Lamb, K.M. / G-Dayanandan, N. / Wright, D.L. / Anderson, A.C.
History
DepositionApr 22, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 9, 2013Provider: repository / Type: Initial release
Revision 1.1Oct 30, 2013Group: Database references
Revision 1.2Nov 20, 2013Group: Non-polymer description
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 / pdbx_struct_conn_angle / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _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: Dihydrofolate reductase
B: Dihydrofolate reductase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)45,32715
Polymers42,6992
Non-polymers2,62813
Water6,251347
1
A: Dihydrofolate reductase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)22,6477
Polymers21,3501
Non-polymers1,2976
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Dihydrofolate reductase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)22,6818
Polymers21,3501
Non-polymers1,3317
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)88.077, 93.634, 96.039
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221
Components on special symmetry positions
IDModelComponents
11A-346-

HOH

21A-405-

HOH

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Dihydrofolate reductase


Mass: 21349.525 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Strain: RP11-399L5 / Gene: DHFR, huDHFR / Plasmid: pET41a(+) / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P00374, dihydrofolate reductase

-
Non-polymers , 5 types, 360 molecules

#2: Chemical ChemComp-NDP / NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE


Mass: 745.421 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H30N7O17P3
#3: Chemical ChemComp-06U / 6-ethyl-5-{(3R)-3-[3-methoxy-5-(pyridin-4-yl)phenyl]but-1-yn-1-yl}pyrimidine-2,4-diamine


Mass: 373.451 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H23N5O
#4: Chemical
ChemComp-EOH / ETHANOL


Mass: 46.068 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C2H6O
#5: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Ca
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 347 / 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: 2.32 Å3/Da / Density % sol: 46.99 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 0.1M Tris-HCl pH 7.4, 0.2M Lithium sulfate, 30% (w/v) PEG 4000, 8% (v/v) ethanol, 11mM CaCl2, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU / Wavelength: 1.5418 Å
DetectorType: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Jun 11, 2011 / Details: Varimax optics
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.8→46.82 Å / Num. all: 37102 / Num. obs: 37016 / % possible obs: 99.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 3.95 % / Biso Wilson estimate: 31.21 Å2 / Rmerge(I) obs: 0.061 / Net I/σ(I): 8.3
Reflection shellResolution: 1.8→1.86 Å / Redundancy: 3.88 % / Rmerge(I) obs: 0.492 / Mean I/σ(I) obs: 1 / Rsym value: 0.554

-
Processing

Software
NameVersionClassification
StructureStudiodata collection
PHASERfor MRphasing
PHENIXrefinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2C2S

2c2s


Resolution: 1.8→32.077 Å / Occupancy max: 1 / Occupancy min: 0.16 / FOM work R set: 0.7549 / SU ML: 0.27 / Phase error: 30.18 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflection
Rfree0.2685 1845 5 %
Rwork0.223 35078 -
obs0.2253 36923 99.55 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 18.1734 Å2
Refinement stepCycle: LAST / Resolution: 1.8→32.077 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3004 0 171 347 3522
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 13

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.8001-1.84870.38691520.331826392791100
1.8487-1.90310.37921360.3312655279199
1.9031-1.96450.33141300.310226912821100
1.9645-2.03470.43511220.307827062828100
2.0347-2.11620.33361290.273726652794100
2.1162-2.21250.30761310.270927122843100
2.2125-2.32910.33511500.27422675282599
2.3291-2.4750.31721490.256226982847100
2.475-2.6660.30961390.250327012840100
2.666-2.93410.30381420.24926922834100
2.9341-3.35830.2861580.218527062864100
3.3583-4.22950.21531600.16662722288299
4.2295-32.08230.18851470.17162816296398

+
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