[English] 日本語
Yorodumi
- PDB-2wrx: Semi-synthetic analogue of human insulin NMeAlaB26-insulin at pH 3.0 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2wrx
TitleSemi-synthetic analogue of human insulin NMeAlaB26-insulin at pH 3.0
Components
  • INSULIN A CHAIN
  • INSULIN B CHAIN
KeywordsHORMONE / CARBOHYDRATE METABOLISM / GLUCOSE METABOLISM / ANALOGUE / DIABETES MELLITUS
Function / homology
Function and homology information


negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / regulation of cellular amino acid metabolic process / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / Signaling by Insulin receptor / nitric oxide-cGMP-mediated signaling / IRS activation / Insulin processing / regulation of protein secretion ...negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / regulation of cellular amino acid metabolic process / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / Signaling by Insulin receptor / nitric oxide-cGMP-mediated signaling / IRS activation / Insulin processing / regulation of protein secretion / positive regulation of peptide hormone secretion / positive regulation of respiratory burst / Regulation of gene expression in beta cells / negative regulation of acute inflammatory response / alpha-beta T cell activation / negative regulation of respiratory burst involved in inflammatory response / positive regulation of dendritic spine maintenance / positive regulation of glycogen biosynthetic process / Synthesis, secretion, and deacylation of Ghrelin / negative regulation of protein secretion / positive regulation of nitric oxide mediated signal transduction / fatty acid homeostasis / regulation of protein localization to plasma membrane / Signal attenuation / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / negative regulation of lipid catabolic process / negative regulation of gluconeogenesis / COPI-mediated anterograde transport / positive regulation of lipid biosynthetic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / negative regulation of reactive oxygen species biosynthetic process / positive regulation of insulin receptor signaling pathway / transport vesicle / positive regulation of protein autophosphorylation / Insulin receptor recycling / insulin-like growth factor receptor binding / neuron projection maintenance / NPAS4 regulates expression of target genes / positive regulation of protein metabolic process / positive regulation of brown fat cell differentiation / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of glycolytic process / activation of protein kinase B activity / positive regulation of mitotic nuclear division / Insulin receptor signalling cascade / positive regulation of cytokine production / positive regulation of long-term synaptic potentiation / Regulation of insulin secretion / acute-phase response / endosome lumen / positive regulation of protein secretion / positive regulation of glucose import / positive regulation of nitric-oxide synthase activity / positive regulation of cell differentiation / negative regulation of proteolysis / regulation of transmembrane transporter activity / wound healing / regulation of synaptic plasticity / insulin receptor binding / negative regulation of protein catabolic process / hormone activity / cognition / positive regulation of neuron projection development / Golgi lumen / positive regulation of protein localization to nucleus / vasodilation / glucose metabolic process / regulation of protein localization / insulin receptor signaling pathway / cell-cell signaling / glucose homeostasis / positive regulation of NF-kappaB transcription factor activity / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / positive regulation of cell growth / secretory granule lumen / protease binding / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of cell migration / G protein-coupled receptor signaling pathway / Amyloid fiber formation / endoplasmic reticulum lumen / Golgi membrane / negative regulation of gene expression / positive regulation of cell population proliferation / regulation of DNA-templated transcription / positive regulation of gene expression / extracellular space / extracellular region / identical protein binding
Similarity search - Function
Insulin / Insulin family / Insulin/IGF/Relaxin family / Insulin, conserved site / Insulin family signature. / Insulin-like / Insulin / insulin-like growth factor / relaxin family. / Insulin-like superfamily
Similarity search - Domain/homology
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.5 Å
AuthorsBrzozowski, A.M. / Jiracek, J. / Zakova, L. / Antolikova, E. / Watson, C.J. / Turkenburg, J.P. / Dodson, G.G.
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2010
Title: Implications for the Active Form of Human Insulin Based on the Structural Convergence of Highly Active Hormone Analogues.
Authors: Jiracek, J. / Zakova, L. / Antolikova, E. / Watson, C.J. / Turkenburg, J.P. / Dodson, G.G. / Brzozowski, A.M.
History
DepositionSep 2, 2009Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 9, 2010Provider: repository / Type: Initial release
Revision 1.1Apr 4, 2012Group: Advisory / Atomic model ...Advisory / Atomic model / Database references / Derived calculations / Non-polymer description / Other / Version format compliance
Revision 1.2Dec 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _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: INSULIN A CHAIN
B: INSULIN B CHAIN
C: INSULIN A CHAIN
D: INSULIN B CHAIN
hetero molecules


Theoretical massNumber of molelcules
Total (without water)11,5025
Polymers11,4794
Non-polymers231
Water1,820101
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3490 Å2
ΔGint-46.3 kcal/mol
Surface area6120 Å2
MethodPISA
Unit cell
Length a, b, c (Å)39.239, 39.239, 124.908
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number92
Space group name H-MP41212

-
Components

#1: Protein/peptide INSULIN A CHAIN


Mass: 2383.698 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) HOMO SAPIENS (human) / References: UniProt: P01308
#2: Protein/peptide INSULIN B CHAIN


Mass: 3355.884 Da / Num. of mol.: 2 / Mutation: YES / Source method: obtained synthetically
Details: METHYLATION OF B26 AND D26 PEPTIDE NITROGEN ATOM IN B AND D CHAIN OF HUMAN INSULIN
Source: (synth.) HOMO SAPIENS (human) / References: UniProt: P01308
#3: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 101 / Source method: isolated from a natural source / Formula: H2O
Compound detailsENGINEERED RESIDUE IN CHAIN B, TYR 50 TO MAA ENGINEERED RESIDUE IN CHAIN D, TYR 50 TO MAA
Nonpolymer detailsSODIUM (NA): SODIUM CATION
Sequence details26 TYR MUTATED TO ALA AND N ATOM OF B26 PEPTIDE IS METHYLATED 26 TYR MUTATED TO ALA AND N ATOM OF ...26 TYR MUTATED TO ALA AND N ATOM OF B26 PEPTIDE IS METHYLATED 26 TYR MUTATED TO ALA AND N ATOM OF D26 PEPTIDE IS METHYLATED

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 2.4 Å3/Da / Density % sol: 48 % / Description: NONE
Crystal growpH: 3 / Details: 0.18 M LI2SO4, 0.1M NA ACETATE PH 3.0

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-1 / Wavelength: 1.0723
DetectorType: ADSC CCD / Detector: CCD / Date: Jan 30, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0723 Å / Relative weight: 1
ReflectionResolution: 1.5→30 Å / Num. obs: 17552 / % possible obs: 94.6 % / Observed criterion σ(I): 0 / Redundancy: 13.4 % / Biso Wilson estimate: 20.2 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 9.2
Reflection shellResolution: 1.5→1.55 Å / Redundancy: 1.5 % / Rmerge(I) obs: 0.47 / Mean I/σ(I) obs: 5.5 / % possible all: 60.5

-
Processing

Software
NameVersionClassification
REFMAC5.5.0082refinement
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1MSO

1mso


Resolution: 1.5→37.42 Å / Cor.coef. Fo:Fc: 0.966 / Cor.coef. Fo:Fc free: 0.948 / SU B: 4.273 / SU ML: 0.069 / Cross valid method: THROUGHOUT / ESU R: 0.096 / ESU R Free: 0.093 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. U VALUES RESIDUAL ONLY. B1 PHE IS NOT MODELLED. B29 LYS AND B30 THR ARE NOT MODELLED. B21 GLU SIDE CHAIN IS MOBILE AND ITS OCCUPANCY IS SET ...Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. U VALUES RESIDUAL ONLY. B1 PHE IS NOT MODELLED. B29 LYS AND B30 THR ARE NOT MODELLED. B21 GLU SIDE CHAIN IS MOBILE AND ITS OCCUPANCY IS SET TO ZERO. B22 ARG SIDE CHAIN IS MOBILE AND ITS OCCUPANCY IS SET TO ZERO. D1 PHE IS NOT MODELLED. D29 LYS AND D30 THR ARE NOT MODELLED. D21 GLU SIDE CHAIN IS MOBILE AND ITS OCCUPANCY IS SET TO ZERO. D22 ARG SIDE CHAIN IS MOBILE AND ITS OCCUPANCY IS SET TO ZERO.
RfactorNum. reflection% reflectionSelection details
Rfree0.25053 787 5 %RANDOM
Rwork0.18019 ---
obs0.18343 14801 94.63 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 17.567 Å2
Baniso -1Baniso -2Baniso -3
1-0.78 Å20 Å20 Å2
2--0.78 Å20 Å2
3----1.55 Å2
Refinement stepCycle: LAST / Resolution: 1.5→37.42 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms742 0 1 101 844
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0230.022767
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.981.9541051
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg9.2225100
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.86225.29434
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.36215114
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.593151
X-RAY DIFFRACTIONr_chiral_restr0.1460.2122
X-RAY DIFFRACTIONr_gen_planes_refined0.010.02581
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.981.5485
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it2.8262777
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it3.8773282
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it5.544.5270
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr2.2913767
X-RAY DIFFRACTIONr_sphericity_free8.4543102
X-RAY DIFFRACTIONr_sphericity_bonded5.5353745
LS refinement shellResolution: 1.5→1.539 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.312 33 -
Rwork0.283 649 -
obs--57.7 %
Refinement TLS params.

T33: 0.0272 Å2 / Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.89-1.03870.31885.8128-1.48723.1336-0.2104-0.07730.03810.25350.30010.1191-0.0732-0.3912-0.08970.06710.0413-0.01360.0871-0.0042.977617.963724.458
21.6061-0.01110.19283.2814-2.20175.0776-0.0731-0.12650.0015-0.25690.1590.16460.3006-0.599-0.08590.0922-0.07-0.00220.1154-0.00831.920219.72968.1554
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A1 - 21
2X-RAY DIFFRACTION1B2 - 29
3X-RAY DIFFRACTION2C1 - 21
4X-RAY DIFFRACTION2D2 - 28

+
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