[English] 日本語
Yorodumi
- PDB-3in7: Crystal Structure of the Grb2 SH2 Domain in Complex with a Cyclop... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3in7
TitleCrystal Structure of the Grb2 SH2 Domain in Complex with a Cyclopropyl-constrained Ac-pY-Q-N-NH2 Tripeptide Mimic
ComponentsGrowth factor receptor-bound protein 2GRB2
KeywordsSIGNALING PROTEIN/PEPTIDE / LIGAND PREORGANIZATION / PEPTIDE MIMICS / Golgi apparatus / Host-virus interaction / Phosphoprotein / SH2 domain / SH3 domain / Signaling protein-pseudopeptide ligand complex / SIGNALING PROTEIN-PEPTIDE COMPLEX
Function / homology
Function and homology information


guanyl-nucleotide exchange factor adaptor activity / Grb2-EGFR complex / branching involved in labyrinthine layer morphogenesis / STAT5 Activation / COP9 signalosome / vesicle membrane / neurotrophin TRKA receptor binding / Activated NTRK2 signals through PI3K / MET receptor recycling / transmembrane receptor protein tyrosine kinase adaptor activity ...guanyl-nucleotide exchange factor adaptor activity / Grb2-EGFR complex / branching involved in labyrinthine layer morphogenesis / STAT5 Activation / COP9 signalosome / vesicle membrane / neurotrophin TRKA receptor binding / Activated NTRK2 signals through PI3K / MET receptor recycling / transmembrane receptor protein tyrosine kinase adaptor activity / Signaling by cytosolic FGFR1 fusion mutants / Interleukin-15 signaling / MET activates PTPN11 / MET activates RAP1 and RAC1 / CD28 dependent Vav1 pathway / Costimulation by the CD28 family / MET activates PI3K/AKT signaling / Signal regulatory protein family interactions / Regulation of KIT signaling / epidermal growth factor receptor binding / positive regulation of actin filament polymerization / PI-3K cascade:FGFR3 / STAT5 activation downstream of FLT3 ITD mutants / PI-3K cascade:FGFR2 / PI-3K cascade:FGFR4 / PI-3K cascade:FGFR1 / endodermal cell differentiation / regulation of MAPK cascade / GRB2:SOS provides linkage to MAPK signaling for Integrins / RHOU GTPase cycle / PI3K events in ERBB2 signaling / Signaling by ALK fusions and activated point mutants / SOS-mediated signalling / Activated NTRK3 signals through RAS / RET signaling / Activated NTRK2 signals through RAS / insulin receptor substrate binding / PI3K Cascade / Interleukin-3, Interleukin-5 and GM-CSF signaling / SHC1 events in ERBB4 signaling / RHO GTPases Activate WASPs and WAVEs / Signalling to RAS / fibroblast growth factor receptor signaling pathway / GAB1 signalosome / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / Role of LAT2/NTAL/LAB on calcium mobilization / Signal attenuation / Interleukin receptor SHC signaling / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / Schwann cell development / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR2 / SHC-mediated cascade:FGFR4 / Signaling by FGFR4 in disease / SHC-mediated cascade:FGFR1 / Erythropoietin activates RAS / signal transduction in response to DNA damage / FRS-mediated FGFR3 signaling / Signaling by CSF3 (G-CSF) / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Signaling by FGFR3 in disease / FRS-mediated FGFR1 signaling / Tie2 Signaling / Signaling by FGFR2 in disease / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / myelination / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / FLT3 Signaling / Signaling by FGFR1 in disease / GRB2 events in ERBB2 signaling / NCAM signaling for neurite out-growth / phosphotyrosine residue binding / ephrin receptor binding / SHC1 events in ERBB2 signaling / Downstream signal transduction / Insulin receptor signalling cascade / Constitutive Signaling by Overexpressed ERBB2 / FCERI mediated Ca+2 mobilization / InlB-mediated entry of Listeria monocytogenes into host cell / insulin-like growth factor receptor signaling pathway / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / cellular response to ionizing radiation / Regulation of signaling by CBL / Negative regulation of FGFR3 signaling / Negative regulation of FGFR2 signaling / FCGR3A-mediated phagocytosis / FCERI mediated MAPK activation / Negative regulation of FGFR4 signaling / EGFR downregulation / Negative regulation of FGFR1 signaling / Signaling by ERBB2 TMD/JMD mutants / B cell receptor signaling pathway
Similarity search - Function
GRB2, N-terminal SH3 domain / GRB2, C-terminal SH3 domain / Grb2-like / SH2 domain / SHC Adaptor Protein / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain ...GRB2, N-terminal SH3 domain / GRB2, C-terminal SH3 domain / Grb2-like / SH2 domain / SHC Adaptor Protein / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / Src homology 3 domains / SH2 domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
CYCLOPROPYL-CONSTRAINED AC-PY-Q-N-NH2 TRIPEPTIDE MIMIC / Chem-AYQ / Growth factor receptor-bound protein 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2 Å
AuthorsClements, J.H.
Citation
Journal: J.Am.Chem.Soc. / Year: 2009
Title: Thermodynamic and Structural Effects of Conformational Constraints in Protein-Ligand Interactions. Entropic Paradoxy Associated with Ligand Preorganization.
Authors: Delorbe, J.E. / Clements, J.H. / Teresk, M.G. / Benfield, A.P. / Plake, H.R. / Millspaugh, L.E. / Martin, S.F.
#1: Journal: Angew.Chem.Int.Ed.Engl. / Year: 2006
Title: Ligand Preorganization May Be Accompanied by Entropic Penalties in Protein-Ligand Interactions
Authors: Benfield, A.P. / Teresk, M.G. / Plake, H.R. / DeLorbe, J.E. / Millspaugh, L.E. / Martin, S.F.
History
DepositionAug 11, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 17, 2009Provider: 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 1.2Dec 12, 2012Group: Other
Revision 1.3Nov 1, 2017Group: Refinement description / Category: software
Revision 1.4Sep 6, 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Growth factor receptor-bound protein 2
C: Growth factor receptor-bound protein 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,6304
Polymers27,5172
Non-polymers1,1132
Water2,144119
1
A: Growth factor receptor-bound protein 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)14,3152
Polymers13,7591
Non-polymers5561
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
C: Growth factor receptor-bound protein 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)14,3152
Polymers13,7591
Non-polymers5561
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2130 Å2
ΔGint-12 kcal/mol
Surface area10300 Å2
MethodPISA
Unit cell
Length a, b, c (Å)40.384, 63.955, 92.725
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Growth factor receptor-bound protein 2 / GRB2 / Adapter protein GRB2 / SH2/SH3 adapter GRB2 / Protein Ash


Mass: 13758.543 Da / Num. of mol.: 2 / Fragment: SH2 domain
Source method: isolated from a genetically manipulated source
Details: residues 53-163 were expressed in addition to a C-terminal 6-his tag
Source: (gene. exp.) Homo sapiens (human) / Gene: GRB2, ASH / Plasmid: pQE-60 / Production host: Escherichia coli (E. coli) / Strain (production host): SG13009 / References: UniProt: P62993
#2: Chemical ChemComp-AYQ / N~2~-({(1R,2R,3S)-2-(methylcarbamoyl)-3-[4-(phosphonooxy)phenyl]cyclopropyl}carbonyl)-D-glutaminyl-D-aspartamide


Type: peptide-like, Peptide-like / Class: Inhibitor / Mass: 556.463 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H29N6O10P
References: CYCLOPROPYL-CONSTRAINED AC-PY-Q-N-NH2 TRIPEPTIDE MIMIC
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 119 / 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: 2.18 Å3/Da / Density % sol: 43.47 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: Ligand in lyophilized powder form was dissolved in a 7.6 mg/mL solution of Grb2 SH2 in water such to give a protein/ligand molar ratio of 1.7:1. 3.5 uL of this solution was mixed with 3.5 uL ...Details: Ligand in lyophilized powder form was dissolved in a 7.6 mg/mL solution of Grb2 SH2 in water such to give a protein/ligand molar ratio of 1.7:1. 3.5 uL of this solution was mixed with 3.5 uL of 0.1 M HEPES, 20% w/v PEG MW10,000, pH 7.5 to create the hanging drop, which yielded crystals of the protein-ligand complex in the presence of the above-mentioned solution after two weeks at room temperature., VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU RU200 / Wavelength: 1.5418 Å
DetectorType: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: May 25, 2007
RadiationMonochromator: blue max-flux confocal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.7→50 Å / Num. all: 27887 / Num. obs: 19967 / % possible obs: 71.6 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 4.5 % / Rmerge(I) obs: 0.054 / Χ2: 1.75 / Net I/σ(I): 20.4
Reflection shellResolution: 1.7→1.76 Å / Redundancy: 1.7 % / Rmerge(I) obs: 0.305 / Num. unique all: 179 / Χ2: 0.989 / % possible all: 6.6

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
CNSrefinement
PDB_EXTRACT3.005data extraction
CrystalCleardata collection
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: pdb entry 2HUW

2huw


Resolution: 2→50 Å / Occupancy max: 1 / Occupancy min: 1 / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.25 709 4.2 %random
Rwork0.229 ---
all-16854 --
obs-14090 83.6 %-
Solvent computationBsol: 20.711 Å2
Displacement parametersBiso max: 64.88 Å2 / Biso mean: 31.558 Å2 / Biso min: 14.71 Å2
Baniso -1Baniso -2Baniso -3
1--14.475 Å20 Å20 Å2
2--7.857 Å20 Å2
3---6.618 Å2
Refinement stepCycle: LAST / Resolution: 2→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1643 0 76 119 1838
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_bond_d0.012
X-RAY DIFFRACTIONc_angle_d1.659
X-RAY DIFFRACTIONc_mcbond_it1.4131.5
X-RAY DIFFRACTIONc_scbond_it1.8812
X-RAY DIFFRACTIONc_mcangle_it2.2682
X-RAY DIFFRACTIONc_scangle_it2.7662.5
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1CNS_TOPPAR:protein_rep.paramCNS_TOPPAR:protein.top
X-RAY DIFFRACTION2CNS_TOPPAR:dna-rna_rep.paramCNS_TOPPAR:dna-rna.top
X-RAY DIFFRACTION3CNS_TOPPAR:water_rep.paramCNS_TOPPAR:water.top
X-RAY DIFFRACTION4CNS_TOPPAR:ion.paramCNS_TOPPAR:ion.top
X-RAY DIFFRACTION5cpYQN.paramcpYQN.top

+
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