[English] 日本語
Yorodumi
- PDB-3kjs: Crystal Structure of T. cruzi DHFR-TS with 3 high affinity DHFR i... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3kjs
TitleCrystal Structure of T. cruzi DHFR-TS with 3 high affinity DHFR inhibitors: DQ1 inhibitor complex
ComponentsDihydrofolate reductase-thymidylate synthase
KeywordsOxidoreductase / Transferase
Function / homology
Function and homology information


thymidylate synthase activity / dTMP biosynthetic process / dihydrofolate reductase activity / tetrahydrofolate biosynthetic process / one-carbon metabolic process / methylation / nucleotide binding
Similarity search - Function
Bifunctional dihydrofolate reductase/thymidylate synthase / Thymidylate Synthase; Chain A / Thymidylate synthase/dCMP hydroxymethylase domain / Thymidylate synthase/dCMP hydroxymethylase / Thymidylate synthase, active site / Thymidylate synthase active site. / Thymidylate synthase / Thymidylate synthase/dCMP hydroxymethylase domain / Thymidylate synthase/dCMP hydroxymethylase superfamily / Thymidylate synthase ...Bifunctional dihydrofolate reductase/thymidylate synthase / Thymidylate Synthase; Chain A / Thymidylate synthase/dCMP hydroxymethylase domain / Thymidylate synthase/dCMP hydroxymethylase / Thymidylate synthase, active site / Thymidylate synthase active site. / Thymidylate synthase / Thymidylate synthase/dCMP hydroxymethylase domain / Thymidylate synthase/dCMP hydroxymethylase superfamily / Thymidylate synthase / Dihydrofolate Reductase, subunit A / Dihydrofolate Reductase, subunit A / Dihydrofolate reductase conserved site / Dihydrofolate reductase (DHFR) domain signature. / Dihydrofolate reductase domain / Dihydrofolate reductase / Dihydrofolate reductase (DHFR) domain profile. / Dihydrofolate reductase-like domain superfamily / 2-Layer Sandwich / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-DQ1 / NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Bifunctional dihydrofolate reductase-thymidylate synthase
Similarity search - Component
Biological speciesTrypanosoma cruzi (eukaryote)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsSchormann, N. / Senkovich, O. / Chattopadhyay, D.
CitationJournal: Bioorg.Med.Chem. / Year: 2010
Title: Synthesis and characterization of potent inhibitors of Trypanosoma cruzi dihydrofolate reductase.
Authors: Schormann, N. / Velu, S.E. / Murugesan, S. / Senkovich, O. / Walker, K. / Chenna, B.C. / Shinkre, B. / Desai, A. / Chattopadhyay, D.
History
DepositionNov 3, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 9, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Sep 6, 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: Dihydrofolate reductase-thymidylate synthase
B: Dihydrofolate reductase-thymidylate synthase
C: Dihydrofolate reductase-thymidylate synthase
D: Dihydrofolate reductase-thymidylate synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)241,86733
Polymers235,6164
Non-polymers6,25129
Water13,277737
1
A: Dihydrofolate reductase-thymidylate synthase
D: Dihydrofolate reductase-thymidylate synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)121,02718
Polymers117,8082
Non-polymers3,21916
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4340 Å2
ΔGint-10 kcal/mol
Surface area42730 Å2
MethodPISA
2
B: Dihydrofolate reductase-thymidylate synthase
C: Dihydrofolate reductase-thymidylate synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)120,84115
Polymers117,8082
Non-polymers3,03213
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4310 Å2
ΔGint-10 kcal/mol
Surface area43540 Å2
MethodPISA
Unit cell
Length a, b, c (Å)175.620, 175.620, 249.905
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number96
Space group name H-MP43212

-
Components

-
Protein , 1 types, 4 molecules ABCD

#1: Protein
Dihydrofolate reductase-thymidylate synthase


Mass: 58904.074 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Trypanosoma cruzi (eukaryote) / Strain: Y / Gene: dhfrts / Plasmid: pET15b / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta(DE3)pLysS
References: UniProt: Q8T5T8, dihydrofolate reductase, thymidylate synthase

-
Non-polymers , 5 types, 766 molecules

#2: Chemical
ChemComp-DQ1 / ethyl 4-(5-{[(2,4-diaminoquinazolin-6-yl)methyl]amino}-2-methoxyphenoxy)butanoate


Mass: 425.481 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C22H27N5O4
#3: Chemical
ChemComp-NAP / NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / 2'-MONOPHOSPHOADENOSINE 5'-DIPHOSPHORIBOSE


Mass: 743.405 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C21H28N7O17P3
#4: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: SO4
#5: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 13 / Source method: obtained synthetically / Formula: C2H6O2
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 737 / 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: 4.11 Å3/Da / Density % sol: 70.08 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 50mM Hepes, pH 7.0, 10mM magnesium chloride, 1.5-1.7M ammonium sulfate, 5-10% ethylene glycol, VAPOR DIFFUSION, HANGING DROP, temperature 298.0K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: MARRESEARCH / Detector: CCD / Date: Aug 15, 2006 / Details: mirrors
RadiationMonochromator: graphite / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.5→20 Å / Num. all: 134571 / Num. obs: 134571 / % possible obs: 99.6 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 4 % / Biso Wilson estimate: 35.3 Å2 / Rmerge(I) obs: 0.06 / Rsym value: 0.06 / Net I/σ(I): 13
Reflection shellResolution: 2.5→2.59 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.256 / Mean I/σ(I) obs: 4 / Rsym value: 0.256 / % possible all: 98.9

-
Processing

Software
NameVersionClassification
HKL-2000data collection
PHASERphasing
REFMAC5.5.0102refinement
d*TREKdata reduction
d*TREKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2H2Q

2h2q


Resolution: 2.5→20 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.926 / SU B: 14.628 / SU ML: 0.153 / Isotropic thermal model: Isotropic / Cross valid method: THROUGHOUT / ESU R: 0.275 / ESU R Free: 0.218 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.23378 6726 5 %RANDOM
Rwork0.19999 ---
obs0.20167 126968 99.57 %-
all-127341 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 41.712 Å2
Baniso -1Baniso -2Baniso -3
1-1.18 Å20 Å20 Å2
2--1.18 Å20 Å2
3----2.36 Å2
Refinement stepCycle: LAST / Resolution: 2.5→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms15905 0 408 737 17050
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.02216700
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.1831.99222681
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.36652003
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.84822.737760
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.648152689
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.59515158
X-RAY DIFFRACTIONr_chiral_restr0.0950.22458
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.02112730
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.3851.510015
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it0.745216157
X-RAY DIFFRACTIONr_scbond_it0.94736685
X-RAY DIFFRACTIONr_scangle_it1.6574.56523
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.5→2.565 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.309 475 -
Rwork0.27 9160 -
obs--99.74 %
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)
10.5133-0.2750.77950.2932-0.36482.0083-0.0684-0.03840.10280.0485-0.0270.061-0.3195-0.2260.09540.09540.02560.01780.1016-0.04240.136531.2520.84548.578
20.52770.2314-0.42580.4815-0.31791.7602-0.0006-0.0611-0.08670.0363-0.02590.130.2873-0.26120.02640.0949-0.05-0.0070.0891-0.01060.115529.252-14.75918.054
30.71560.33760.6760.81350.72591.9355-0.06110.0380.1057-0.07310.0047-0.0661-0.26210.18670.05650.0417-0.02510.00370.03150.0240.063959.62420.08318.774
40.5392-0.2743-0.44880.82440.6931.7648-0.0232-0.0414-0.07410.0505-0.021-0.05050.24970.13110.04430.05630.0112-0.00110.03640.0350.053557.587-16.63347.937
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A2 - 232
2X-RAY DIFFRACTION1A233 - 515
3X-RAY DIFFRACTION2B3 - 232
4X-RAY DIFFRACTION2B233 - 515
5X-RAY DIFFRACTION3C2 - 232
6X-RAY DIFFRACTION3C233 - 515
7X-RAY DIFFRACTION4D2 - 232
8X-RAY DIFFRACTION4D233 - 515

+
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