4G0V

Human topoisomerase iibeta in complex with DNA and mitoxantrone

> Summary

Summary for 4G0V

Related3QX3 4G0U 4G0W 4J3N
DescriptorDNA topoisomerase 2-beta (E.C.5.99.1.3)/DNA complex, Mitoxantrone
Functional Keywordstoprim domain, winged-helix domain, coiled-coil domain, dna-binding and cleavage, nucleus, isomerase-dna-isomerase inhibitor complex, isomerase/dna/isomerase inhibitor
Biological sourceHomo sapiens (human)
Cellular locationCytoplasm Q02880
Total number of polymer chains6
Total molecular weight197075.21
Authors
Wu, C.C.,Li, T.K.,Li, Y.C.,Chan, N.L. (deposition date: 2012-07-10, release date: 2013-07-17, modification date: 2014-03-12)
Primary citation
Wu, C.C.,Li, Y.C.,Wang, Y.R.,Li, T.K.,Chan, N.L.
On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs
Nucleic Acids Res., 41:10630-10640, 2013
PubMed: 24038465
DOI: 10.1093/nar/gkt828
MImport into Mendeley
Experimental method
X-RAY DIFFRACTION (2.548 Å)
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Structure validation

RfreeClashscoreRamachandran outliersSidechain outliersRSRZ outliers0.20540.2%0.7%3.9%MetricValuePercentile RanksWorseBetterPercentile relative to all X-ray structuresPercentile relative to X-ray structures of similar resolution

More Asymmetric unit images

Molmil generated image of 4g0v
no rotation
Molmil generated image of 4g0v
rotated about x axis by 90°
Molmil generated image of 4g0v
rotated about y axis by 90°

> Structural details

Entity

Chain IDDescriptionTypeChain lengthFormula weightNumber of moleculesDB Name (Accession)Biological sourceDescriptive keywords
A, BDNA topoisomerase 2-betapolymer80391929.22
UniProt (Q02880)
Pfam (PF00204)
Pfam (PF00521)
Pfam (PF01751)
Pfam (PF16898)
Homo sapiens (human)@PDBjDNA topoisomerase II, beta isozyme
C, EDNA (5'-D(P*AP*GP*CP*CP*GP*AP*GP*C)-3')polymer82436.62
D, FDNA (5'-D(P*TP*GP*CP*AP*GP*CP*TP*CP*GP*GP*CP*T)-3')polymer123654.42
1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONEnon-polymer444.52
MAGNESIUM IONnon-polymer24.36
waterwater18.0559

Sequence viewer

Contents of the asymmetric unit

PolymersNumber of chains6
Total molecular weight196040.4
Non-Polymers*Number of molecules8
Total molecular weight1034.8
All*Total molecular weight197075.2
*Water molecules are not included.

> Experimental details

Refinement Statistics

Experimental method:X-RAY DIFFRACTION (2.548 Å)

Cell axes80.546176.61093.759
Cell angles90.00111.5390.00
SpacegroupP 1 21 1
Resolution limits27.94 - 2.55
the highest resolution shell value2.638 - 2.548
R-factor0.1631
R-work0.16080
the highest resolution shell value0.220
R-free0.20600
the highest resolution shell value0.286
RMSD bond length0.008
RMSD bond angle1.122

Data Collection Statistics

Resolution limits30.00 - 2.55
the highest resolution shell value -
Number of reflections78830
the highest resolution shell value0.490
Completeness99.4
Redundancy3.6
the highest resolution shell value3.5
I/sigma(I)1

Crystallization Conditions

crystal IDmethodpHpH rangetemperatureunit
1VAPOR DIFFUSION, HANGING DROP5.8277

Crystallization Reagents

IDcrystal IDsolution IDreagent nameconcentrationdetails
Crystallization Reagents in Literatures*
IDcrystal IDsolutionreagent nameconcentration (unit)details
Annotated Information is extracted from Literature Info*

> Functional details

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Functional Information from GO Data

ChainGOidnamespacecontents
A0005737cellular_componentcytoplasm
A0005829cellular_componentcytosol
A0009330cellular_componentDNA topoisomerase complex (ATP-hydrolyzing)
A0005654cellular_componentnucleoplasm
A0005634cellular_componentnucleus
A0005524molecular_functionATP binding
A0003682molecular_functionchromatin binding
A0008301molecular_functionDNA binding, bending
A0003918molecular_functionDNA topoisomerase type II (ATP-hydrolyzing) activity
A0019899molecular_functionenzyme binding
A0042826molecular_functionhistone deacetylase binding
A0046872molecular_functionmetal ion binding
A0008022molecular_functionprotein C-terminus binding
A0046982molecular_functionprotein heterodimerization activity
A0005080molecular_functionprotein kinase C binding
A0007409biological_processaxonogenesis
A0006265biological_processDNA topological change
A0006268biological_processDNA unwinding involved in DNA replication
A0030900biological_processforebrain development
A0044774biological_processmitotic DNA integrity checkpoint
A0006312biological_processmitotic recombination
A0001764biological_processneuron migration
A0016925biological_processprotein sumoylation
A0000712biological_processresolution of meiotic recombination intermediates
A0000819biological_processsister chromatid segregation
B0005737cellular_componentcytoplasm
B0005829cellular_componentcytosol
B0009330cellular_componentDNA topoisomerase complex (ATP-hydrolyzing)
B0005654cellular_componentnucleoplasm
B0005634cellular_componentnucleus
B0005524molecular_functionATP binding
B0003682molecular_functionchromatin binding
B0008301molecular_functionDNA binding, bending
B0003918molecular_functionDNA topoisomerase type II (ATP-hydrolyzing) activity
B0019899molecular_functionenzyme binding
B0042826molecular_functionhistone deacetylase binding
B0046872molecular_functionmetal ion binding
B0008022molecular_functionprotein C-terminus binding
B0046982molecular_functionprotein heterodimerization activity
B0005080molecular_functionprotein kinase C binding
B0007409biological_processaxonogenesis
B0006265biological_processDNA topological change
B0006268biological_processDNA unwinding involved in DNA replication
B0030900biological_processforebrain development
B0044774biological_processmitotic DNA integrity checkpoint
B0006312biological_processmitotic recombination
B0001764biological_processneuron migration
B0016925biological_processprotein sumoylation
B0000712biological_processresolution of meiotic recombination intermediates
B0000819biological_processsister chromatid segregation
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Functional Information from PDB Data

site_idNumber of ResiduesDetails
AC113BINDING SITE FOR RESIDUE MIX A 1301
ChainResidue
AARG503
AGLY504
ALYS505
AILE506
AASN520
AGLU522
AGLN778
AMET782
CDC8
DDT9
FDA12
FDG13
FDC14

AC22BINDING SITE FOR RESIDUE MG A 1302
ChainResidue
AASP557
AASP559

AC32BINDING SITE FOR RESIDUE MG A 1303
ChainResidue
AASN795
AASN867

AC42BINDING SITE FOR RESIDUE MG B 1301
ChainResidue
BASP557
BASP559

AC52BINDING SITE FOR RESIDUE MG B 1302
ChainResidue
BASN795
BASN867

AC611BINDING SITE FOR RESIDUE MIX D 101
ChainResidue
BARG503
BGLY504
BLYS505
BASN520
BGLU522
BGLN778
DDA12
DDG13
DDC14
EDC8
FDT9

AC70BINDING SITE FOR RESIDUE MG D 102
ChainResidue

AC80BINDING SITE FOR RESIDUE MG F 101
ChainResidue

10
ChainResidue

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Functional Information from PDB atom coordinates for the "HETATM" binding sites

site_idNumber of ResiduesDetails
MIX_4g0v_A_1301151,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE binding site
ChainResidueligand
AARG503-LEU507MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
AASN520MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
AGLU522MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
AGLN778MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
AMET782MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
CDG7-DC8MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
DDT9MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
FDA12-DC14MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE

MIX_4g0v_D_101151,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE binding site
ChainResidueligand
BARG503-LEU507MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
BASN520MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
BGLU522MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
BGLN778MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
BMET782MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
DDA12-DC8MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE
FDT9MIX: 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE

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Functional Information from PROSITE/UniProt

site_idNumber of ResiduesDetails
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Functional Information from SwissProt/UniProt

site_idNumber of ResiduesDetails
SWS_FT_FI11O-(5'-phospho-DNA)-tyrosine intermediate.
ChainResidueDetails
ATYR403

SWS_FT_FI42ATP (By similarity).
ChainResidueDetails
ANA*
ANA*

SWS_FT_FI93ATP (By similarity).
ChainResidueDetails
ANA*
ANA*
ANA*

SWS_FT_FI101O-(5'-phospho-DNA)-tyrosine intermediate.
ChainResidueDetails
BTYR403

SWS_FT_FI132ATP (By similarity).
ChainResidueDetails
BNA*
BNA*

SWS_FT_FI183ATP (By similarity).
ChainResidueDetails
BNA*
BNA*
BNA*

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Catalytic Information from CSA

site_idNumber of ResiduesDetails

> Sequence Neighbor

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