[English] 日本語
Yorodumi
- PDB-2wrw: Semi-synthetic highly active analogue of human insulin D-ProB26-D... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2wrw
TitleSemi-synthetic highly active analogue of human insulin D-ProB26-DTI- NH2
Components
  • INSULIN A CHAIN
  • INSULIN B CHAIN
KeywordsHORMONE / CARBOHYDRATE METABOLISM / GLUCOSE METABOLISM / ANALOGUE / DIABETES MELLITUS
Function / homology
Function and homology information


negative regulation of glycogen catabolic process / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / Signaling by Insulin receptor / IRS activation / regulation of protein secretion / Insulin processing / positive regulation of peptide hormone secretion / positive regulation of respiratory burst ...negative regulation of glycogen catabolic process / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / Signaling by Insulin receptor / IRS activation / regulation of protein secretion / Insulin processing / positive regulation of peptide hormone secretion / positive regulation of respiratory burst / negative regulation of acute inflammatory response / Regulation of gene expression in beta cells / alpha-beta T cell activation / positive regulation of dendritic spine maintenance / Synthesis, secretion, and deacylation of Ghrelin / negative regulation of respiratory burst involved in inflammatory response / activation of protein kinase B activity / negative regulation of protein secretion / negative regulation of gluconeogenesis / positive regulation of insulin receptor signaling pathway / positive regulation of glycogen biosynthetic process / fatty acid homeostasis / Signal attenuation / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / negative regulation of lipid catabolic process / positive regulation of lipid biosynthetic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / regulation of protein localization to plasma membrane / nitric oxide-cGMP-mediated signaling / transport vesicle / COPI-mediated anterograde transport / positive regulation of nitric-oxide synthase activity / Insulin receptor recycling / negative regulation of reactive oxygen species biosynthetic process / insulin-like growth factor receptor binding / positive regulation of brown fat cell differentiation / NPAS4 regulates expression of target genes / neuron projection maintenance / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of mitotic nuclear division / Insulin receptor signalling cascade / positive regulation of glycolytic process / positive regulation of cytokine production / endosome lumen / positive regulation of long-term synaptic potentiation / acute-phase response / positive regulation of protein secretion / positive regulation of D-glucose import / insulin receptor binding / positive regulation of cell differentiation / Regulation of insulin secretion / wound healing / positive regulation of neuron projection development / hormone activity / negative regulation of protein catabolic process / regulation of synaptic plasticity / positive regulation of protein localization to nucleus / Golgi lumen / vasodilation / cognition / glucose metabolic process / insulin receptor signaling pathway / glucose homeostasis / cell-cell signaling / regulation of protein localization / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / positive regulation of cell growth / protease binding / secretory granule lumen / positive regulation of canonical NF-kappaB signal transduction / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of MAPK cascade / positive regulation of cell migration / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / Amyloid fiber formation / Golgi membrane / negative regulation of gene expression / positive regulation of cell population proliferation / positive regulation of gene expression / regulation of DNA-templated transcription / extracellular space / extracellular region / identical protein binding
Similarity search - Function
Insulin / Insulin family / Insulin-like / Insulin/IGF/Relaxin family / Insulin / insulin-like growth factor / relaxin family. / Insulin, conserved site / Insulin family signature. / Insulin-like superfamily
Similarity search - Domain/homology
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.41 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 1.1Jul 13, 2011Group: Advisory / Version format compliance
Revision 1.2Jun 6, 2012Group: Other
Revision 1.3Dec 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 / struct_conn
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 / _struct_conn.pdbx_leaving_atom_flag

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: INSULIN A CHAIN
B: INSULIN B CHAIN


Theoretical massNumber of molelcules
Total (without water)5,3222
Polymers5,3222
Non-polymers00
Water45025
1
A: INSULIN A CHAIN
B: INSULIN B CHAIN

A: INSULIN A CHAIN
B: INSULIN B CHAIN


Theoretical massNumber of molelcules
Total (without water)10,6444
Polymers10,6444
Non-polymers00
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation8_555-y,-x,-z1
Buried area3500 Å2
ΔGint-37.3 kcal/mol
Surface area5770 Å2
MethodPISA
Unit cell
Length a, b, c (Å)39.372, 39.372, 123.928
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number98
Space group name H-MI4122
Components on special symmetry positions
IDModelComponents
11A-2006-

HOH

-
Components

#1: Protein/peptide INSULIN A CHAIN


Mass: 2383.698 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) HOMO SAPIENS (human) / References: UniProt: P01308
#2: Protein/peptide INSULIN B CHAIN


Mass: 2938.408 Da / Num. of mol.: 1 / Fragment: RESIDUES 25-50 / Mutation: YES / Source method: obtained synthetically / Source: (synth.) HOMO SAPIENS (human) / References: UniProt: P01308
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 25 / Source method: isolated from a natural source / Formula: H2O
Compound detailsENGINEERED RESIDUE IN CHAIN B, TYR 50 TO PR9
Sequence detailsB26 TYR MUTATED TO D-PRO B27-B30 ARE DELETED B26 C- TERMINUS IS FINISHED WITH CONH2 (CARBOXYAMIDE) ...B26 TYR MUTATED TO D-PRO B27-B30 ARE DELETED B26 C- TERMINUS IS FINISHED WITH CONH2 (CARBOXYAMIDE) NOT A COOH GROUP

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 2.3 Å3/Da / Density % sol: 46 % / Description: NONE
Crystal growpH: 3 / Details: 0.015 M CS2SO4 PH 3.0

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-2 / Wavelength: 0.933
DetectorType: ADSC CCD / Detector: CCD / Date: Feb 19, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.933 Å / Relative weight: 1
ReflectionResolution: 2.41→50 Å / Num. obs: 2438 / % possible obs: 98.5 % / Observed criterion σ(I): 0 / Redundancy: 6 % / Biso Wilson estimate: 36.2 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 14.6
Reflection shellResolution: 2.41→2.45 Å / Redundancy: 5 % / Rmerge(I) obs: 0.22 / Mean I/σ(I) obs: 9.2 / % possible all: 98.1

-
Processing

Software
NameVersionClassification
REFMAC5.5.0088refinement
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1MSO

1mso


Resolution: 2.41→25 Å / Cor.coef. Fo:Fc: 0.92 / Cor.coef. Fo:Fc free: 0.824 / SU B: 24.583 / SU ML: 0.245 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / ESU R: 0.505 / ESU R Free: 0.321 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. B26 TYR MUTATED TO D-PRO. B27-B30 ARE DELETED. B26 C-TERMINUS IS FINISHED WITH CONH2 (CARBOXYAMIDE), NOT A COOH GROUP. PHE B1 IS NOT MODELLED (DISORDERED).
RfactorNum. reflection% reflectionSelection details
Rfree0.30086 93 4.5 %RANDOM
Rwork0.23653 ---
obs0.23931 1977 98.48 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 6.928 Å2
Baniso -1Baniso -2Baniso -3
1-0.52 Å20 Å20 Å2
2--0.52 Å20 Å2
3----1.04 Å2
Refinement stepCycle: LAST / Resolution: 2.41→25 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms359 0 0 25 384
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0170.021353
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.6321.96480
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.813544
X-RAY DIFFRACTIONr_dihedral_angle_2_deg50.13726.2516
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.8391553
X-RAY DIFFRACTIONr_dihedral_angle_4_deg
X-RAY DIFFRACTIONr_chiral_restr0.0920.254
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.02270
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_it0.7231.5226
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.3412359
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it1.8473127
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it3.2134.5121
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.41→2.472 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.197 6 -
Rwork0.292 133 -
obs--95.21 %
Refinement TLS params.Method: refined / Origin x: -7.1265 Å / Origin y: 11.1984 Å / Origin z: 6.9934 Å
111213212223313233
T0.1516 Å2-0.0279 Å20.0032 Å2-0.1144 Å20.0469 Å2--0.1494 Å2
L2.3013 °21.9406 °2-0.5547 °2-1.7603 °2-1.3 °2--6.0825 °2
S-0.1481 Å °0.1694 Å °-0.0897 Å °-0.1332 Å °0.2183 Å °-0.0367 Å °0.1682 Å °-0.4422 Å °-0.0703 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A1 - 21
2X-RAY DIFFRACTION1B1 - 26

+
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