[English] 日本語
Yorodumi
- PDB-4x20: Discovery of cytotoxic Dolastatin 10 analogs with N-terminal modi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4x20
TitleDiscovery of cytotoxic Dolastatin 10 analogs with N-terminal modifications
Components
  • Stathmin-4
  • Tubulin alpha chain
  • Tubulin beta chain
KeywordsStructural Protein/Inhibitor / Binding Sites / Competitive / Cattle / Tumor / Colchicine / Humans / Microtubules / Protein Binding / Protein Conformation / Protein Multimerization / Tubulin / Tubulin Modulators / Structural Protein-Inhibitor complex
Function / homology
Function and homology information


axonemal microtubule / organelle transport along microtubule / forebrain morphogenesis / cerebellar cortex morphogenesis / glial cell differentiation / dentate gyrus development / neuron projection arborization / flagellated sperm motility / response to L-glutamate / pyramidal neuron differentiation ...axonemal microtubule / organelle transport along microtubule / forebrain morphogenesis / cerebellar cortex morphogenesis / glial cell differentiation / dentate gyrus development / neuron projection arborization / flagellated sperm motility / response to L-glutamate / pyramidal neuron differentiation / microtubule depolymerization / centrosome cycle / smoothened signaling pathway / regulation of synapse organization / startle response / motor behavior / response to tumor necrosis factor / locomotory exploration behavior / microtubule polymerization / regulation of microtubule polymerization or depolymerization / sperm flagellum / response to mechanical stimulus / microtubule-based process / condensed chromosome / homeostasis of number of cells within a tissue / tubulin binding / cellular response to calcium ion / adult locomotory behavior / neuromuscular junction / intracellular protein transport / synapse organization / recycling endosome / cerebral cortex development / visual learning / structural constituent of cytoskeleton / memory / cytoplasmic ribonucleoprotein granule / neuron migration / neuron projection development / growth cone / neuron apoptotic process / gene expression / microtubule / hydrolase activity / neuron projection / protein heterodimerization activity / GTPase activity / GTP binding / protein-containing complex binding / Golgi apparatus / metal ion binding / identical protein binding / plasma membrane / cytoplasm / cytosol
Similarity search - Function
Methane Monooxygenase Hydroxylase; Chain G, domain 1 - #30 / Methane Monooxygenase Hydroxylase; Chain G, domain 1 / Helix hairpin bin / Stathmin family / Stathmin, conserved site / Stathmin superfamily / Stathmin family / Stathmin family signature 1. / Stathmin family signature 2. / Stathmin-like (SLD) domain profile. ...Methane Monooxygenase Hydroxylase; Chain G, domain 1 - #30 / Methane Monooxygenase Hydroxylase; Chain G, domain 1 / Helix hairpin bin / Stathmin family / Stathmin, conserved site / Stathmin superfamily / Stathmin family / Stathmin family signature 1. / Stathmin family signature 2. / Stathmin-like (SLD) domain profile. / Tubulin/FtsZ, C-terminal domain / Tubulin/FtsZ, GTPase domain / 60s Ribosomal Protein L30; Chain: A; / Alpha tubulin / Tubulin-beta mRNA autoregulation signal. / Beta tubulin, autoregulation binding site / Beta tubulin / Tubulin / Tubulin, C-terminal / Tubulin C-terminal domain / Tubulin, conserved site / Tubulin subunits alpha, beta, and gamma signature. / Tubulin/FtsZ family, C-terminal domain / Tubulin/FtsZ-like, C-terminal domain / Tubulin/FtsZ, C-terminal / Tubulin/FtsZ, 2-layer sandwich domain / Tubulin/FtsZ family, GTPase domain / Tubulin/FtsZ family, GTPase domain / Tubulin/FtsZ, GTPase domain / Tubulin/FtsZ, GTPase domain superfamily / Helix non-globular / Special / Helix Hairpins / Rossmann fold / 2-Layer Sandwich / Orthogonal Bundle / 3-Layer(aba) Sandwich / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
2-methyl-L-prolyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S)-1-carboxy-2-phenylethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide / Chem-3WY / GUANOSINE-5'-DIPHOSPHATE / GUANOSINE-5'-TRIPHOSPHATE / Chem-LOC / Tubulin beta chain / Tubulin alpha chain / Stathmin-4
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
Ovis aries (sheep)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.5 Å
AuthorsParris, K.D.
CitationJournal: J.Med.Chem. / Year: 2014
Title: Discovery of cytotoxic dolastatin 10 analogues with N-terminal modifications.
Authors: Maderna, A. / Doroski, M. / Subramanyam, C. / Porte, A. / Leverett, C.A. / Vetelino, B.C. / Chen, Z. / Risley, H. / Parris, K. / Pandit, J. / Varghese, A.H. / Shanker, S. / Song, C. / ...Authors: Maderna, A. / Doroski, M. / Subramanyam, C. / Porte, A. / Leverett, C.A. / Vetelino, B.C. / Chen, Z. / Risley, H. / Parris, K. / Pandit, J. / Varghese, A.H. / Shanker, S. / Song, C. / Sukuru, S.C. / Farley, K.A. / Wagenaar, M.M. / Shapiro, M.J. / Musto, S. / Lam, M.H. / Loganzo, F. / O'Donnell, C.J.
History
DepositionNov 25, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 25, 2015Provider: repository / Type: Initial release
Revision 1.1Apr 8, 2015Group: Non-polymer description
Revision 1.2Sep 27, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description / Source and taxonomy
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / database_2 / entity_src_gen / entity_src_nat / pdbx_initial_refinement_model / pdbx_struct_oper_list
Item: _citation.journal_id_CSD / _database_2.pdbx_DOI ..._citation.journal_id_CSD / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity_src_gen.pdbx_alt_source_flag / _entity_src_nat.pdbx_alt_source_flag / _pdbx_struct_oper_list.symmetry_operation

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Tubulin alpha chain
B: Tubulin beta chain
C: Tubulin alpha chain
D: Tubulin beta chain
E: Stathmin-4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)221,27715
Polymers217,0365
Non-polymers4,24010
Water00
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area18400 Å2
ΔGint-105 kcal/mol
Surface area65380 Å2
MethodPISA
Unit cell
Length a, b, c (Å)66.240, 128.270, 254.140
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 3 types, 5 molecules ACBDE

#1: Protein Tubulin alpha chain


Mass: 50188.441 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Ovis aries (sheep) / References: UniProt: D0VWZ0
#2: Protein Tubulin beta chain


Mass: 49969.797 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Ovis aries (sheep) / References: UniProt: D0VWY9
#3: Protein Stathmin-4 / Stathmin-like protein B3 / RB3


Mass: 16719.938 Da / Num. of mol.: 1 / Fragment: UNP residues 49-189
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Stmn4 / Production host: Escherichia coli (E. coli) / References: UniProt: P63043

-
Non-polymers , 5 types, 10 molecules

#4: Chemical ChemComp-GTP / GUANOSINE-5'-TRIPHOSPHATE


Mass: 523.180 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Formula: C10H16N5O14P3 / Comment: GTP, energy-carrying molecule*YM
#5: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#6: Chemical ChemComp-GDP / GUANOSINE-5'-DIPHOSPHATE


Type: RNA linking / Mass: 443.201 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H15N5O11P2 / Comment: GDP, energy-carrying molecule*YM
#7: Chemical ChemComp-LOC / N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[d]heptalen-7-yl]ethanamide / COLCHICINE


Mass: 399.437 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H25NO6
#8: Chemical ChemComp-3WY / 2-methyl-L-prolyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S)-1-carboxy-2-phenylethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide


Type: peptide-like, Peptide-like / Class: Inhibitor / Mass: 729.946 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C39H63N5O8
References: 2-methyl-L-prolyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S)-1-carboxy-2-phenylethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.62 Å3/Da / Density % sol: 53.05 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 6.8
Details: 5% PEG 400, 0.1M LiSO4, 5-7% PEG 20K, 50 mM K-PIPES

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 9, 2012
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3.5→50 Å / Num. obs: 25405 / % possible obs: 90.1 % / Redundancy: 4 % / Biso Wilson estimate: 106.47 Å2 / Rmerge(I) obs: 0.12 / Χ2: 0.821 / Net I/av σ(I): 11.087 / Net I/σ(I): 3.7 / Num. measured all: 101790
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2% possible all
3.5-3.563.20.99311900.46387.6
3.56-3.633.30.9912330.48689.3
3.63-3.693.50.85912900.4890.8
3.69-3.773.80.68212620.49493.3
3.77-3.8540.61812560.47991.8
3.85-3.944.10.53513040.51192.4
3.94-4.044.10.43812770.52692.9
4.04-4.154.20.32913170.51293.1
4.15-4.274.20.26912590.55291.7
4.27-4.4140.22412980.6292
4.41-4.573.90.17212530.73391.1
4.57-4.754.20.16112910.69990
4.75-4.974.20.14112210.77488.2
4.97-5.234.30.14512690.73491.4
5.23-5.554.30.1413100.69190.5
5.55-5.984.20.13112790.76490.5
5.98-6.5840.11412630.81688.3
6.58-7.534.10.09512561.20387.2
7.53-9.484.30.07713041.83788.4
9.48-5040.07212732.73981.8

-
Processing

Software
NameVersionClassification
BUSTER2.11.5refinement
DENZOdata reduction
PDB_EXTRACT3.15data extraction
SCALEPACKdata scaling
BUSTERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3HKB

3hkb


Resolution: 3.5→40.83 Å / Cor.coef. Fo:Fc: 0.9136 / Cor.coef. Fo:Fc free: 0.8925 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.682
RfactorNum. reflection% reflectionSelection details
Rfree0.2519 1289 5.08 %RANDOM
Rwork0.1807 ---
obs0.1845 25352 90.17 %-
Displacement parametersBiso mean: 147.36 Å2
Baniso -1Baniso -2Baniso -3
1--74.7958 Å20 Å20 Å2
2--33.55 Å20 Å2
3---41.2458 Å2
Refine analyzeLuzzati coordinate error obs: 0.798 Å
Refinement stepCycle: LAST / Resolution: 3.5→40.83 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms14448 0 284 0 14732
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0115018HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.2420372HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d5244SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes401HARMONIC2
X-RAY DIFFRACTIONt_gen_planes2288HARMONIC5
X-RAY DIFFRACTIONt_it15018HARMONIC20
X-RAY DIFFRACTIONt_nbd73SEMIHARMONIC5
X-RAY DIFFRACTIONt_omega_torsion2.58
X-RAY DIFFRACTIONt_other_torsion24.73
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion1952SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact18284SEMIHARMONIC4
LS refinement shellResolution: 3.5→3.64 Å / Total num. of bins used: 13
RfactorNum. reflection% reflection
Rfree0.303 143 5.19 %
Rwork0.2448 2611 -
all0.2479 2754 -
obs--90.17 %

+
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