|Entry||Database: PDB / ID: 6ver|
|Title||Human insulin analog: [GluB10,TyrB20]-DOI|
|Function / homology|
Function and homology information
Signaling by Insulin receptor / negative regulation of glycogen catabolic process / alpha-beta T cell activation / Insulin processing / IRS activation / Insulin receptor recycling / negative regulation of NAD(P)H oxidase activity / nitric oxide-cGMP-mediated signaling pathway / negative regulation of feeding behavior / negative regulation of fatty acid metabolic process ...Signaling by Insulin receptor / negative regulation of glycogen catabolic process / alpha-beta T cell activation / Insulin processing / IRS activation / Insulin receptor recycling / negative regulation of NAD(P)H oxidase activity / nitric oxide-cGMP-mediated signaling pathway / negative regulation of feeding behavior / negative regulation of fatty acid metabolic process / regulation of protein secretion / Regulation of gene expression in beta cells / positive regulation of peptide hormone secretion / positive regulation of respiratory burst / negative regulation of respiratory burst involved in inflammatory response / negative regulation of gluconeogenesis / negative regulation of reactive oxygen species biosynthetic process / positive regulation of cellular protein metabolic process / regulation of protein localization to plasma membrane / COPI-mediated anterograde transport / Regulation of insulin secretion / positive regulation of dendritic spine maintenance / Synthesis, secretion, and deacylation of Ghrelin / positive regulation of glycogen biosynthetic process / regulation of cellular amino acid metabolic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / positive regulation of nitric oxide mediated signal transduction / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / Signal attenuation / negative regulation of lipid catabolic process / negative regulation of protein secretion / positive regulation of lipid biosynthetic process / fatty acid homeostasis / endosome lumen / transport vesicle / positive regulation of insulin receptor signaling pathway / endoplasmic reticulum-Golgi intermediate compartment membrane / neuron projection maintenance / insulin-like growth factor receptor binding / positive regulation of protein autophosphorylation / positive regulation of glycolytic process / negative regulation of acute inflammatory response / regulation of transmembrane transporter activity / positive regulation of cell differentiation / Insulin receptor signalling cascade / positive regulation of mitotic nuclear division / regulation of synaptic plasticity / positive regulation of brown fat cell differentiation / cognition / regulation of protein localization / positive regulation of long-term synaptic potentiation / positive regulation of cytokine production / acute-phase response / activation of protein kinase B activity / positive regulation of glucose import / vasodilation / hormone activity / negative regulation of proteolysis / negative regulation of protein catabolic process / insulin receptor binding / positive regulation of protein localization to nucleus / insulin receptor signaling pathway / glucose metabolic process / Golgi lumen / positive regulation of nitric-oxide synthase activity / cell-cell signaling / glucose homeostasis / wound healing / endoplasmic reticulum to Golgi vesicle-mediated transport / positive regulation of MAPK cascade / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / positive regulation of phosphatidylinositol 3-kinase signaling / positive regulation of cell growth / secretory granule lumen / protease binding / positive regulation of NF-kappaB transcription factor activity / positive regulation of cell migration / positive regulation of protein kinase B signaling / Amyloid fiber formation / Golgi membrane / G protein-coupled receptor signaling pathway / amyloid fibril formation / endoplasmic reticulum lumen / regulation of transcription, DNA-templated / positive regulation of gene expression / positive regulation of cell population proliferation / extracellular space / extracellular region / identical protein binding
Similarity search - Function
Insulin / Insulin family / Insulin-like / Insulin / insulin-like growth factor / relaxin family. / Insulin/IGF/Relaxin family / Insulin, conserved site / Insulin-like superfamily / Insulin family signature.
Similarity search - Domain/homology
|Biological species||Homo sapiens (human)|
|Method||X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.047 Å|
|Authors||Menting, J.G. / Chou, D.H.-C. / Lawrence, M.C. / Xiong, X.|
|Funding support|| Australia, United States, 2items |
|Citation||Journal: not published|
Title: Mini-Ins: A minimal, bioactive insulin analog with alternative binding modes
Authors: Xiong, X. / Menting, J. / Disotaur, M. / Agrawal, R. / Delaine, C. / MacRaild, C. / Ghabash, G. / Kim, J.H. / Olivera, B. / Safavi, H. / Norton, R. / Forbes, B. / Fisher, S. / Lawrence, M.C. / Chou, D.
|Structure viewer||Molecule: |
Downloads & links
A: Insulin A chain
B: Insulin B chain
|#1: Protein/peptide|| |
Mass: 2383.698 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P01308
|#2: Protein/peptide|| |
Mass: 2587.967 Da / Num. of mol.: 1 / Mutation: H10E, G20Y / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P01308
|#3: Water|| ChemComp-HOH / |
|Experiment||Method: X-RAY DIFFRACTION / Number of used crystals: 1|
|Crystal||Density Matthews: 1.82 Å3/Da / Density % sol: 32.43 %|
|Crystal grow||Temperature: 300 K / Method: vapor diffusion, sitting drop|
Details: Well condition: 100 mM Tri-HCl (pH 8.5) + 0.28 M magnesium formate. Protein: The insulin analog was prepared in a mixture that also contained receptor fragments: 5 mg/ml (IR310.T).Fv83-7 in ...Details: Well condition: 100 mM Tri-HCl (pH 8.5) + 0.28 M magnesium formate. Protein: The insulin analog was prepared in a mixture that also contained receptor fragments: 5 mg/ml (IR310.T).Fv83-7 in 10mM HEPES-NaOH (pH7.5) + 0.02% NaN3 plus three mol equivalents of the IR-A alphaCT peptide 704-719 plus 1.8 mol equivalents of the analog. The analog crystallized in isolation from the receptor fragments and it is not known whether the receptor fragments aided crystallization
|Diffraction||Mean temperature: 100 K / Serial crystal experiment: N|
|Diffraction source||Source: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.95364 Å|
|Detector||Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Mar 22, 2017|
|Radiation||Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray|
|Radiation wavelength||Wavelength: 0.95364 Å / Relative weight: 1|
|Reflection||Resolution: 1.047→44.86 Å / Num. obs: 17679 / % possible obs: 99.8 % / Redundancy: 6 % / CC1/2: 0.999 / Rmerge(I) obs: 0.036 / Rpim(I) all: 0.017 / Rrim(I) all: 0.04 / Net I/σ(I): 21.9|
|Reflection shell||Resolution: 1.047→1.06 Å / Redundancy: 4.5 % / Rmerge(I) obs: 0.857 / Num. unique obs: 836 / CC1/2: 0.735 / Rpim(I) all: 0.442 / Rrim(I) all: 0.969 / Rsym value: 0.442 / % possible all: 98.4|
|Refinement||Method to determine structure: MOLECULAR REPLACEMENT|
Starting model: Editted version of human insulin component of PDB entry 4OGA
Resolution: 1.047→24.933 Å / SU ML: 0.12 / Cross valid method: FREE R-VALUE / σ(F): 1.37 / Phase error: 21.25
|Solvent computation||Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å|
|Refinement step||Cycle: LAST / Resolution: 1.047→24.933 Å|
|Refine LS restraints|
|LS refinement shell|
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