[English] 日本語
Yorodumi
- PDB-4hof: Candida albicans dihydrofolate reductase complexed with NADPH and... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4hof
TitleCandida albicans dihydrofolate reductase complexed with NADPH and 5-[3-(2-methoxy-4-phenylphenyl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine (UCP111H)
ComponentsDihydrofolate reductase
KeywordsOXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / Antifungal Agents / Candida albicans / Drug Design / Enzyme Inhibitors / Fungal Proteins / Structure-Activity Relationship / Tetrahydrofolate Dehydrogenase / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex
Function / homology
Function and homology information


dihydrofolate metabolic process / dihydrofolate reductase / dihydrofolate reductase activity / folic acid metabolic process / tetrahydrofolate biosynthetic process / one-carbon metabolic process / NADP binding / mitochondrion
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-18H / GLYCINE / Chem-NDP / Dihydrofolate reductase
Similarity search - Component
Biological speciesCandida albicans (yeast)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.76 Å
AuthorsPaulsen, J.L. / Anderson, A.C.
CitationJournal: J.Med.Chem. / Year: 2014
Title: Propargyl-Linked Antifolates are Dual Inhibitors of Candida albicans and Candida glabrata.
Authors: G-Dayanandan, N. / Paulsen, J.L. / Viswanathan, K. / Keshipeddy, S. / Lombardo, M.N. / Zhou, W. / Lamb, K.M. / Sochia, A.E. / Alverson, J.B. / Priestley, N.D. / Wright, D.L. / Anderson, A.C.
History
DepositionOct 22, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 19, 2014Provider: repository / Type: Initial release
Revision 1.1Apr 9, 2014Group: Database references
Revision 1.2Nov 15, 2017Group: Refinement description / Category: software / Item: _software.name
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 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Remark 650HELIX DETERMINATION METHOD: AUTHOR DETERMINED

-
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)47,04011
Polymers44,3892
Non-polymers2,6519
Water6,251347
1
A: Dihydrofolate reductase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)23,6507
Polymers22,1951
Non-polymers1,4556
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Dihydrofolate reductase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)23,3904
Polymers22,1951
Non-polymers1,1963
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)37.931, 66.662, 75.417
Angle α, β, γ (deg.)90.00, 93.13, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Dihydrofolate reductase


Mass: 22194.527 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Candida albicans (yeast) / Gene: DFR1, DHFR / Plasmid: pET41 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P22906, dihydrofolate reductase

-
Non-polymers , 5 types, 356 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-18H / 5-[3-(2-methoxy-4-phenylphenyl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine / 5-[(3S)-3-(3-methoxybiphenyl-4-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine


Mass: 358.436 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H22N4O
#4: Chemical ChemComp-GLY / GLYCINE


Type: peptide linking / Mass: 75.067 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H5NO2
#5: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C3H8O3
#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: 2.14 Å3/Da / Density % sol: 42.65 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6.5
Details: PEG 3350, KMES, glycine, pH 6.5, vapor diffusion, hanging drop, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: NSLS / Beamline: X4A / Wavelength: 0.97916 Å
DetectorType: ADSC QUANTUM 4r / Detector: CCD / Date: Jun 26, 2012 / Details: mirrors
RadiationMonochromator: SAGITALLY FOCUSED Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97916 Å / Relative weight: 1
ReflectionResolution: 1.76→50 Å / Num. all: 37060 / Num. obs: 37060 / % possible obs: 99.7 % / Observed criterion σ(F): 3 / Observed criterion σ(I): 3 / Redundancy: 4 % / Rmerge(I) obs: 0.07 / Χ2: 3.455 / Net I/σ(I): 18.7
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
1.76-1.793.90.20318222.678199.1
1.79-1.8240.17618472.816199.9
1.82-1.8640.15818352.9971100
1.86-1.940.14318833.081199.9
1.9-1.9440.13618073.2681100
1.94-1.9840.12418713.459199.9
1.98-2.0340.11418333.3181100
2.03-2.0940.10618713.4761100
2.09-2.1540.09718343.472199.8
2.15-2.2240.09418743.6211100
2.22-2.340.08618303.6251100
2.3-2.3940.08418623.5651100
2.39-2.540.07918403.6541100
2.5-2.634.10.07418503.5921100
2.63-2.7940.06918943.531100
2.79-3.014.10.06218323.416199.9
3.01-3.314.10.05518793.373199.9
3.31-3.7940.05318723.643199.7
3.79-4.783.90.05518744.159199
4.78-503.50.05518504.504196.8

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
SCALEPACKdata scaling
PHASERphasing
REFMAC5.6.0117refinement
PDB_EXTRACT3.11data extraction
HKL-2000data collection
DENZOdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1AOE

1aoe


Resolution: 1.76→20.44 Å / Cor.coef. Fo:Fc: 0.952 / Cor.coef. Fo:Fc free: 0.935 / Occupancy max: 1 / Occupancy min: 0.25 / SU B: 2.264 / SU ML: 0.075 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.136 / ESU R Free: 0.119 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2059 1845 5 %RANDOM
Rwork0.1798 ---
all0.2059 37042 --
obs0.1812 37042 99.56 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 39.75 Å2 / Biso mean: 15.2527 Å2 / Biso min: 7.5 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refinement stepCycle: LAST / Resolution: 1.76→20.44 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3128 0 179 347 3654
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0060.023399
X-RAY DIFFRACTIONr_angle_refined_deg1.3052.0354624
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.8415386
X-RAY DIFFRACTIONr_dihedral_angle_2_deg38.18924.085142
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.50615601
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.2391522
X-RAY DIFFRACTIONr_chiral_restr0.080.2516
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0212487
LS refinement shellResolution: 1.761→1.807 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.223 129 -
Rwork0.208 2444 -
all-2573 -
obs--97.39 %

+
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