[English] 日本語
Yorodumi
- PDB-1ol1: Cyclin A binding groove inhibitor H-Cit-Cit-Leu-Ile-(p-F-Phe)-NH2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1ol1
TitleCyclin A binding groove inhibitor H-Cit-Cit-Leu-Ile-(p-F-Phe)-NH2
Components
  • CELL DIVISION PROTEIN KINASE 2
  • CIR-CIR-LEU-ILE-PFF-NH2
  • CYCLIN A2
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX / CELL CYCLE / KINASE-CYCLIN COMPLEX / CYCLIN A / INHIBITOR / LIGAND EXCHANGE / DRUG DESIGN / SERINE/THREONINE-PROTEIN KINASE / ATP-BINDING / CELL DIVISION / MITOSIS / PHOSPHORYLATION / PEPTIDOMIMETICS
Function / homology
Function and homology information


DNA Damage/Telomere Stress Induced Senescence / G0 and Early G1 / Senescence-Associated Secretory Phenotype (SASP) / SCF(Skp2)-mediated degradation of p27/p21 / Regulation of APC/C activators between G1/S and early anaphase / Activation of ATR in response to replication stress / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / Ub-specific processing proteases ...DNA Damage/Telomere Stress Induced Senescence / G0 and Early G1 / Senescence-Associated Secretory Phenotype (SASP) / SCF(Skp2)-mediated degradation of p27/p21 / Regulation of APC/C activators between G1/S and early anaphase / Activation of ATR in response to replication stress / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / Ub-specific processing proteases / Processing of DNA double-strand break ends / Factors involved in megakaryocyte development and platelet production / Transcriptional regulation of granulopoiesis / Meiotic recombination / PTK6 Regulates Cell Cycle / Cyclin A:Cdk2-associated events at S phase entry / p53-Dependent G1 DNA Damage Response / Cyclin A/B1/B2 associated events during G2/M transition / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Cyclin E associated events during G1/S transition / Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes / CDK-mediated phosphorylation and removal of Cdc6 / Activation of the pre-replicative complex / Orc1 removal from chromatin / G2 Phase / Regulation of TP53 Degradation / Regulation of TP53 Activity through Phosphorylation / cellular response to luteinizing hormone stimulus / cellular response to cocaine / cell cycle G1/S phase transition / mitotic cell cycle phase transition / male pronucleus / female pronucleus / cellular response to insulin-like growth factor stimulus / cellular response to leptin stimulus / response to glucagon / cyclin-dependent protein serine/threonine kinase regulator activity / cochlea development / cellular response to platelet-derived growth factor stimulus / regulation of DNA replication / regulation of cyclin-dependent protein serine/threonine kinase activity / cyclin A1-CDK2 complex / cyclin E1-CDK2 complex / cyclin E2-CDK2 complex / positive regulation of DNA-dependent DNA replication initiation / cyclin A2-CDK2 complex / Y chromosome / cyclin-dependent protein kinase activity / X chromosome / histone phosphorylation / centrosome duplication / centriole replication / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / cyclin-dependent protein kinase holoenzyme complex / condensed chromosome / Cajal body / cellular response to nitric oxide / mitotic G1 DNA damage checkpoint / cyclin binding / regulation of gene silencing / potassium ion transport / meiotic cell cycle / cellular response to estradiol stimulus / chromosome, telomeric region / animal organ regeneration / G1/S transition of mitotic cell cycle / positive regulation of fibroblast proliferation / regulation of G2/M transition of mitotic cell cycle / anaphase-promoting complex-dependent catabolic process / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / cellular response to hypoxia / Ras protein signal transduction / G2/M transition of mitotic cell cycle / transcription factor complex / regulation of signal transduction by p53 class mediator / DNA replication / endosome / peptidyl-serine phosphorylation / protein deubiquitination / centrosome / cell division / DNA repair / protein domain specific binding / viral process / protein serine/threonine kinase activity / protein phosphorylation / positive regulation of cell population proliferation / protein kinase binding / positive regulation of transcription, DNA-templated / magnesium ion binding / negative regulation of transcription by RNA polymerase II / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
Cyclin / Protein kinase-like domain superfamily / Protein kinase domain / Protein kinase, ATP binding site / Protein kinase domain profile. / Cyclins signature. / Serine/Threonine protein kinases active-site signature. / Protein kinases ATP-binding region signature. / N-terminal region of cyclin_N / Cyclin, C-terminal domain ...Cyclin / Protein kinase-like domain superfamily / Protein kinase domain / Protein kinase, ATP binding site / Protein kinase domain profile. / Cyclins signature. / Serine/Threonine protein kinases active-site signature. / Protein kinases ATP-binding region signature. / N-terminal region of cyclin_N / Cyclin, C-terminal domain / Cyclin, N-terminal domain / Serine/threonine-protein kinase, active site / Cyclin-like / Cyclin, N-terminal / Cyclin, C-terminal domain / Cyclin-like superfamily / Cyclin-A, N-terminal / Protein kinase domain
Cyclin-A2 / Cyclin-dependent kinase 2
Biological speciesHOMO SAPIENS (human)
SYNTHETIC CONSTRUCT (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.9 Å
AuthorsKontopidis, G. / Andrews, M. / McInnes, C. / Cowan, A. / Powers, H. / Innes, L. / Plater, A. / Griffiths, G. / Paterson, D. / Zheleva, D. / Lane, D. / Green, S. / Walkinshaw, M. / Fischer, P.
CitationJournal: Structure / Year: 2003
Title: Insights Into Cyclin Groove Recognition. Complex Crystal Structures and Inhibitor Design Through Ligand Exchange
Authors: Kontopidis, G. / Andrews, M. / Mcinnes, C. / Cowan, A. / Powers, H. / Innes, L. / Plater, A. / Griffiths, G. / Paterson, D. / Zheleva, D. / Lane, D. / Green, S. / Walkinshaw, M. / Fischer, P.
Validation Report
SummaryFull reportAbout validation report
History
DepositionAug 4, 2003Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 11, 2003Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Atomic model / Database references ...Atomic model / Database references / Derived calculations / Non-polymer description / Structure summary / Version format compliance
Revision 1.2Feb 15, 2017Group: Database references / Source and taxonomy

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: CELL DIVISION PROTEIN KINASE 2
B: CYCLIN A2
C: CELL DIVISION PROTEIN KINASE 2
D: CYCLIN A2
F: CIR-CIR-LEU-ILE-PFF-NH2
H: CIR-CIR-LEU-ILE-PFF-NH2


Theoretical massNumber of molelcules
Total (without water)129,1326
Polymers129,1326
Non-polymers00
Water1,31573
1
A: CELL DIVISION PROTEIN KINASE 2
B: CYCLIN A2
F: CIR-CIR-LEU-ILE-PFF-NH2


Theoretical massNumber of molelcules
Total (without water)64,5663
Polymers64,5663
Non-polymers00
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4700 Å2
ΔGint-10 kcal/mol
Surface area23570 Å2
MethodPISA
2
C: CELL DIVISION PROTEIN KINASE 2
D: CYCLIN A2
H: CIR-CIR-LEU-ILE-PFF-NH2


Theoretical massNumber of molelcules
Total (without water)64,5663
Polymers64,5663
Non-polymers00
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4780 Å2
ΔGint-5 kcal/mol
Surface area23490 Å2
MethodPISA
Unit cell
γ
α
β
Length a, b, c (Å)74.498, 113.471, 154.482
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein/peptide CELL DIVISION PROTEIN KINASE 2 / / CYCLIN-DEPENDENT KINASE 2 / P33 PROTEIN KINASE


Mass: 33976.488 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / References: UniProt: P24941, EC: 2.7.1.37
#2: Protein/peptide CYCLIN A2 / / CYCLIN A


Mass: 29867.512 Da / Num. of mol.: 2 / Fragment: RESIDUES 173 - 432
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / References: UniProt: P20248
#3: Protein/peptide CIR-CIR-LEU-ILE-PFF-NH2


Mass: 721.845 Da / Num. of mol.: 2
Details: CYCLIN GROOVE-BOUND PEPTIDE CIT-CIT-LEU-ILE-PFF-NH2
Source method: obtained synthetically / Source: (synth.) SYNTHETIC CONSTRUCT (others)
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 73 / Source method: isolated from a natural source / Formula: H2O / Water
Compound detailsFUNCTION: INVOLVED IN THE CONTROL OF THE CELL CYCLE. ACTIVITY OF CDK2 IS MAXIMAL DURING S PHASE AND G2.

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.7 Å3/Da / Density % sol: 54 %
Crystal growpH: 7.8 / Details: 22% PEG 3350, 0.1M NA3-CIT, PH 7.80
Crystal grow
*PLUS
pH: 7 / Method: vapor diffusion, hanging drop
Components of the solutions
*PLUS

Crystal-ID: 1

IDConc.Common nameSol-IDDetailsChemical formula
17-8 mg/mlproteindrop
240 mMHEPESdroppH7.0
3200 mMdropNaCl
45 mMdithiothreitoldrop
518 %PEG3350reservoir
6100 mMtrisodium citratereservoir

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-2 / Wavelength: 0.933
DetectorType: ADSC CCD / Detector: CCD / Date: Nov 15, 2002 / Details: MIRRORS
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.933 Å / Relative weight: 1
ReflectionResolution: 2.9→15 Å / Num. obs: 29357 / % possible obs: 98.9 % / Redundancy: 22.5 % / Rmerge(I) obs: 0.12 / Net I/σ(I): 2.8
Reflection shellResolution: 2.9→3.06 Å / Rmerge(I) obs: 0.461 / Mean I/σ(I) obs: 1.5 / % possible all: 98.9
Reflection
*PLUS
Highest resolution: 2.9 Å / Num. measured all: 648091 / Rmerge(I) obs: 0.12
Reflection shell
*PLUS
Highest resolution: 2.9 Å / Rmerge(I) obs: 0.46 / Mean I/σ(I) obs: 1.5

-
Processing

Software
NameVersionClassification
REFMAC5refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1FIN
Resolution: 2.9→12 Å / Cor.coef. Fo:Fc: 0.93 / Cor.coef. Fo:Fc free: 0.863 / SU B: 20.707 / SU ML: 0.399 / Cross valid method: THROUGHOUT / ESU R Free: 0.49 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.284 1198 4.1 %RANDOM
Rwork0.206 ---
Obs0.209 27895 99.4 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BULK SOLVENT
Displacement parametersBiso mean: 52.14 Å2
Baniso -1Baniso -2Baniso -3
1--3.91 Å20 Å20 Å2
2--1.73 Å20 Å2
3---2.15 Å2
Refinement stepCycle: LAST / Resolution: 2.9→12 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9025 0 0 73 9098
Refine LS restraints

Refinement-ID: X-RAY DIFFRACTION

TypeDev idealDev ideal targetNumber
r_bond_refined_d0.0140.0229249
r_bond_other_d0.0020.028494
r_angle_refined_deg1.4191.9812555
r_angle_other_deg1.16319820
r_dihedral_angle_1_deg11.41751104
r_dihedral_angle_2_deg
r_dihedral_angle_3_deg
r_dihedral_angle_4_deg
r_chiral_restr0.1010.21424
r_gen_planes_refined0.0130.029990
r_gen_planes_other0.0070.021806
r_nbd_refined0.3310.33024
r_nbd_other0.3310.311318
r_nbtor_refined
r_nbtor_other0.10.55588
r_xyhbond_nbd_refined0.3050.5557
r_xyhbond_nbd_other
r_metal_ion_refined
r_metal_ion_other
r_symmetry_vdw_refined0.2830.340
r_symmetry_vdw_other0.3370.370
r_symmetry_hbond_refined0.5070.59
r_symmetry_hbond_other
r_symmetry_metal_ion_refined
r_symmetry_metal_ion_other
r_mcbond_it4.3931.55553
r_mcbond_other
r_mcangle_it6.9129031
r_mcangle_other
r_scbond_it9.55233696
r_scbond_other
r_scangle_it14.0984.53524
r_scangle_other
r_long_range_B_refined
r_long_range_B_other
r_rigid_bond_restr
r_sphericity_free
r_sphericity_bonded
LS refinement shellResolution: 2.9→2.97 Å / Total num. of bins used: 20 /
RfactorNum. reflection
Rfree0.418 81
Rwork0.291 1950
Refinement
*PLUS
Rfactor Rfree: 0.291 / Rfactor Rwork: 0.202

+
About Yorodumi

-
News

-
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. (see PDBe EMDB page)
  • 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 at PDBe / 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. See below links for details.
  • 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

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.: Omokage search

+
Sep 15, 2016. EM Navigator & Yorodumi renewed

EM Navigator & Yorodumi renewed

  • New versions of EM Navigator and Yorodumi started

Related info.: Changes in new EM Navigator and Yorodumi

+
Aug 31, 2016. New EM Navigator & Yorodumi

New EM Navigator & Yorodumi

  • In 15th Sep 2016, the development versions of EM Navigator and Yorodumi will replace the official versions.
  • Current version will continue as 'legacy version' for some time.

Related info.: Changes in new EM Navigator and Yorodumi / EM Navigator / Yorodumi

Read more

-
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.

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