[English] 日本語
Yorodumi
- PDB-1urc: Cyclin A binding groove inhibitor Ace-Arg-Lys-Leu-Phe-Gly -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1urc
TitleCyclin A binding groove inhibitor Ace-Arg-Lys-Leu-Phe-Gly
Components
  • CELL DIVISION PROTEIN KINASE 2
  • CYCLIN A2
  • PEPTIDE INHIBITOR
KeywordsTRANSFERASE/INHIBITOR / TRANSFERASE-INHIBITOR COMPLEX / INHIBITOR / LIGAND EXCHANGE / DRUG DESIGN / PEPTIDOMIMETICS
Function / homology
Function and homology information


: / cyclin A2-CDK1 complex / cell cycle G1/S phase transition / cellular response to luteinizing hormone stimulus / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / cellular response to leptin stimulus / male pronucleus / female pronucleus / cellular response to cocaine / response to glucagon ...: / cyclin A2-CDK1 complex / cell cycle G1/S phase transition / cellular response to luteinizing hormone stimulus / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / cellular response to leptin stimulus / male pronucleus / female pronucleus / cellular response to cocaine / response to glucagon / positive regulation of DNA biosynthetic process / cyclin-dependent protein serine/threonine kinase regulator activity / cellular response to insulin-like growth factor stimulus / cyclin A1-CDK2 complex / cyclin E2-CDK2 complex / cyclin E1-CDK2 complex / cyclin A2-CDK2 complex / positive regulation of DNA-templated DNA replication initiation / G2 Phase / Y chromosome / cyclin-dependent protein kinase activity / Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes / positive regulation of heterochromatin formation / p53-Dependent G1 DNA Damage Response / X chromosome / PTK6 Regulates Cell Cycle / regulation of anaphase-promoting complex-dependent catabolic process / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / centriole replication / Regulation of APC/C activators between G1/S and early anaphase / microtubule organizing center / regulation of DNA replication / telomere maintenance in response to DNA damage / centrosome duplication / G0 and Early G1 / cochlea development / Telomere Extension By Telomerase / animal organ regeneration / Activation of the pre-replicative complex / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Cajal body / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / Activation of ATR in response to replication stress / Cyclin E associated events during G1/S transition / Cyclin A/B1/B2 associated events during G2/M transition / Cyclin A:Cdk2-associated events at S phase entry / cyclin-dependent protein kinase holoenzyme complex / condensed chromosome / regulation of G2/M transition of mitotic cell cycle / cellular response to platelet-derived growth factor stimulus / mitotic G1 DNA damage checkpoint signaling / cellular response to nitric oxide / post-translational protein modification / cyclin binding / regulation of mitotic cell cycle / positive regulation of DNA replication / meiotic cell cycle / male germ cell nucleus / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / cellular response to estradiol stimulus / G1/S transition of mitotic cell cycle / peptidyl-serine phosphorylation / DNA Damage/Telomere Stress Induced Senescence / potassium ion transport / CDK-mediated phosphorylation and removal of Cdc6 / Meiotic recombination / SCF(Skp2)-mediated degradation of p27/p21 / G2/M transition of mitotic cell cycle / Orc1 removal from chromatin / Transcriptional regulation of granulopoiesis / positive regulation of fibroblast proliferation / Cyclin D associated events in G1 / cellular senescence / Regulation of TP53 Degradation / nuclear envelope / Factors involved in megakaryocyte development and platelet production / Processing of DNA double-strand break ends / regulation of gene expression / Senescence-Associated Secretory Phenotype (SASP) / transcription regulator complex / cellular response to hypoxia / Regulation of TP53 Activity through Phosphorylation / Ras protein signal transduction / chromosome, telomeric region / DNA replication / protein phosphorylation / endosome / Ub-specific processing proteases / chromatin remodeling / protein domain specific binding / cell division / protein serine kinase activity / DNA repair / protein serine/threonine kinase activity / positive regulation of cell population proliferation / DNA-templated transcription / centrosome / protein kinase binding
Similarity search - Function
Cyclin-A, N-terminal APC/C binding region / Cyclin-A N-terminal APC/C binding region / : / Cyclin, C-terminal domain / : / Cyclins signature. / Cyclin / Cyclin-like / Cyclin, C-terminal domain / Cyclin_C ...Cyclin-A, N-terminal APC/C binding region / Cyclin-A N-terminal APC/C binding region / : / Cyclin, C-terminal domain / : / Cyclins signature. / Cyclin / Cyclin-like / Cyclin, C-terminal domain / Cyclin_C / Cyclin A; domain 1 / Cyclin, N-terminal / Cyclin, N-terminal domain / Cyclin-like / domain present in cyclins, TFIIB and Retinoblastoma / Cyclin-like superfamily / : / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Cyclin-A2 / Cyclin-dependent kinase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.6 Å
AuthorsKontopidis, G. / Andrews, M. / McInnes, C. / Cowan, A. / Powers, H. / Innes, L. / Plater, A. / Griffiths, G. / Paterson, D. / Zheleva, D. ...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.
CitationJournal: Org. Biomol. Chem. / Year: 2004
Title: Design, synthesis, biological activity and structural analysis of cyclic peptide inhibitors targeting the substrate recruitment site of cyclin-dependent kinase complexes.
Authors: Andrews, M.J. / McInnes, C. / Kontopidis, G. / Innes, L. / Cowan, A. / Plater, A. / Fischer, P.M.
History
DepositionOct 28, 2003Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 31, 2003Provider: repository / Type: Initial release
Revision 1.1Sep 4, 2013Group: Database references / Derived calculations ...Database references / Derived calculations / Non-polymer description / Other / Source and taxonomy / Structure summary / Version format compliance
Revision 2.0Mar 7, 2018Group: Atomic model / Database references / Source and taxonomy
Category: atom_site / citation ...atom_site / citation / citation_author / entity_src_gen / pdbx_entity_src_syn
Item: _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ..._atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _citation.journal_abbrev / _citation.page_last / _citation.title / _citation_author.name / _entity_src_gen.gene_src_common_name / _entity_src_gen.pdbx_gene_src_scientific_name / _entity_src_gen.pdbx_host_org_scientific_name / _pdbx_entity_src_syn.ncbi_taxonomy_id / _pdbx_entity_src_syn.organism_scientific
Revision 2.1Oct 9, 2019Group: Advisory / Data collection ...Advisory / Data collection / Derived calculations / Other
Category: pdbx_database_status / pdbx_validate_close_contact / struct_conn
Item: _pdbx_database_status.status_code_sf
Revision 2.2Dec 13, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 2.3Nov 20, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
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
E: PEPTIDE INHIBITOR
F: PEPTIDE INHIBITOR


Theoretical massNumber of molelcules
Total (without water)128,9846
Polymers128,9846
Non-polymers00
Water6,089338
1
A: CELL DIVISION PROTEIN KINASE 2
B: CYCLIN A2
E: PEPTIDE INHIBITOR


Theoretical massNumber of molelcules
Total (without water)64,4923
Polymers64,4923
Non-polymers00
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4230 Å2
ΔGint-23.1 kcal/mol
Surface area23440 Å2
MethodPISA
2
C: CELL DIVISION PROTEIN KINASE 2
D: CYCLIN A2
F: PEPTIDE INHIBITOR


Theoretical massNumber of molelcules
Total (without water)64,4923
Polymers64,4923
Non-polymers00
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4100 Å2
ΔGint-19.5 kcal/mol
Surface area23610 Å2
MethodPISA
Unit cell
Length a, b, c (Å)73.630, 113.510, 155.460
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein CELL DIVISION PROTEIN KINASE 2 / P33 PROTEIN KINASE / CDK2 / CYCLIN-DEPENDENT KINASE-2


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, cyclin-dependent kinase
#2: Protein CYCLIN A2 / CYCLIN A / CCNA2 / CCNA / CCN1


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 PEPTIDE INHIBITOR


Mass: 647.810 Da / Num. of mol.: 2 / Source method: obtained synthetically
Details: CYCLIN GROOVE-BOUND CYCLIC(2-5) PENTAPEPTIDE AC-ARG-LYS-LEU-PHE-GLY
Source: (synth.) synthetic construct (others)
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 338 / Source method: isolated from a natural source / Formula: H2O
Compound detailsCYCLIN CONTROLS THE CELL CYCLE AT THE G1/S (START) AND THE G2/M (MITOSIS) TRANSITIONS. KINASE ...CYCLIN CONTROLS THE CELL CYCLE AT THE G1/S (START) AND THE G2/M (MITOSIS) TRANSITIONS. KINASE INTERACTS WITH CYCLINS A, D, OR E. ACTIVITY OF CDK2 IS MAXIMAL DURING S PHASE AND G2.
Has protein modificationY

-
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
Temperature: 17 ℃ / pH: 7 / Method: vapor diffusion, hanging drop / Details: Kontopidis, G., (2003) Structure, 11, 1537.
Components of the solutions
*PLUS
IDConc.Common nameCrystal-IDSol-IDDetailsChemical formula
17-8 mg/mlprotein1drop
240 mMHEPES1droppH7.0
3200 mM1dropNaCl
45 mMdithiothreitol1drop
518 %PEG33501reservoir
6100 mMtrisodium citrate1reservoir

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SRS / Beamline: PX14.1 / Wavelength: 1.488
DetectorType: ADSC CCD / Detector: CCD / Date: Oct 15, 2002 / Details: MIRRORS
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.488 Å / Relative weight: 1
ReflectionResolution: 2.6→17 Å / Num. obs: 39765 / % possible obs: 99.5 % / Redundancy: 14.2 % / Rmerge(I) obs: 0.11 / Net I/σ(I): 5.8
Reflection shellResolution: 2.6→2.76 Å / Rmerge(I) obs: 0.62 / Mean I/σ(I) obs: 1 / % possible all: 99.4
Reflection
*PLUS
Highest resolution: 2.6 Å / Num. obs: 46681 / % possible obs: 98.9 % / Num. measured all: 113421 / Rmerge(I) obs: 0.11
Reflection shell
*PLUS
Highest resolution: 2.6 Å / Lowest resolution: 2.74 Å / Rmerge(I) obs: 0.52 / Mean I/σ(I) obs: 1

-
Processing

Software
NameClassification
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1FIN

1fin


Resolution: 2.6→14 Å / SU B: 12.153 / SU ML: 0.25 / Cross valid method: THROUGHOUT / ESU R: 1.013 / ESU R Free: 0.327 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.254 1272 3.1 %RANDOM
Rwork0.175 ---
obs0.177 39372 98.9 %-
Displacement parametersBiso mean: 42.1 Å2
Baniso -1Baniso -2Baniso -3
1--2.9 Å20 Å20 Å2
2---0.69 Å20 Å2
3---3.58 Å2
Refinement stepCycle: LAST / Resolution: 2.6→14 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9016 0 0 338 9354
Refinement
*PLUS
Rfactor Rfree: 0.255
Solvent computation
*PLUS
Displacement parameters
*PLUS

+
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