|Entry||Database: PDB / ID: 4p65|
|Title||Crystal structure of an cyclohexylalanine substituted insulin analog.|
|Components||(Insulin) x 2|
|Keywords||HORMONE / protein hormone / non-standard mutagenesis|
|Function / homology|
Function and homology information
Signaling by Insulin receptor / negative regulation of glycogen catabolic process / alpha-beta T cell activation / regulation of cellular amino acid metabolic process / IRS activation / Insulin processing / Insulin receptor recycling / negative regulation of NAD(P)H oxidase activity / nitric oxide-cGMP-mediated signaling pathway / negative regulation of fatty acid metabolic process ...Signaling by Insulin receptor / negative regulation of glycogen catabolic process / alpha-beta T cell activation / regulation of cellular amino acid metabolic process / IRS activation / Insulin processing / Insulin receptor recycling / negative regulation of NAD(P)H oxidase activity / nitric oxide-cGMP-mediated signaling pathway / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / regulation of protein secretion / Regulation of gene expression in beta cells / positive regulation of respiratory burst / positive regulation of peptide hormone secretion / negative regulation of respiratory burst involved in inflammatory response / negative regulation of gluconeogenesis / positive regulation of protein metabolic process => GO:0051247 / negative regulation of acute inflammatory response / positive regulation of dendritic spine maintenance / Synthesis, secretion, and deacylation of Ghrelin / COPI-mediated anterograde transport / positive regulation of glycogen biosynthetic process / regulation of protein localization to plasma membrane / negative regulation of reactive oxygen species biosynthetic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / Signal attenuation / negative regulation of protein secretion / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / positive regulation of nitric oxide mediated signal transduction / positive regulation of lipid biosynthetic process / negative regulation of lipid catabolic process / fatty acid homeostasis / endosome lumen / Regulation of insulin secretion / positive regulation of insulin receptor signaling pathway / endoplasmic reticulum-Golgi intermediate compartment membrane / neuron projection maintenance / transport vesicle / insulin-like growth factor receptor binding / positive regulation of protein autophosphorylation / positive regulation of glycolytic process / Insulin receptor signalling cascade / positive regulation of brown fat cell differentiation / positive regulation of mitotic nuclear division / positive regulation of cell differentiation / regulation of transmembrane transporter activity / positive regulation of long-term synaptic potentiation / regulation of synaptic plasticity / cognition / activation of protein kinase B activity / positive regulation of cytokine production / positive regulation of protein secretion / positive regulation of glucose import / positive regulation of nitric-oxide synthase activity / acute-phase response / negative regulation of proteolysis / hormone activity / vasodilation / insulin receptor binding / insulin receptor signaling pathway / negative regulation of protein catabolic process / positive regulation of protein localization to nucleus / wound healing / Golgi lumen / glucose metabolic process / regulation of protein localization / cell-cell signaling / glucose homeostasis / positive regulation of phosphatidylinositol 3-kinase signaling / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / positive regulation of cell growth / secretory granule lumen / positive regulation of NF-kappaB transcription factor activity / positive regulation of protein kinase B signaling / protease binding / positive regulation of MAPK cascade / G protein-coupled receptor signaling pathway / positive regulation of cell migration / Amyloid fiber formation / Golgi membrane / negative regulation of gene expression / endoplasmic reticulum lumen / positive regulation of cell population proliferation / positive regulation of gene expression / regulation of transcription, DNA-templated / extracellular space / extracellular region / identical protein binding
Similarity search - Function
Insulin / Insulin family / Insulin / insulin-like growth factor / relaxin family. / Insulin/IGF/Relaxin family / Insulin-like / Insulin family signature. / Insulin-like superfamily / Insulin, conserved site
Similarity search - Domain/homology
PHENOL / Insulin
Similarity search - Component
|Biological species||Homo sapiens (human)|
|Method||X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.5 Å|
|Authors||Pandyarajan, V. / Wan, Z. / Weiss, M.A.|
|Citation||Journal: J.Biol.Chem. / Year: 2014|
Title: Aromatic Anchor at an Invariant Hormone-Receptor Interface: FUNCTION OF INSULIN RESIDUE B24 WITH APPLICATION TO PROTEIN DESIGN.
Authors: Pandyarajan, V. / Smith, B.J. / Phillips, N.B. / Whittaker, L. / Cox, G.P. / Wickramasinghe, N. / Menting, J.G. / Wan, Z.L. / Whittaker, J. / Ismail-Beigi, F. / Lawrence, M.C. / Weiss, M.A.
|Structure viewer||Molecule: |
Downloads & links
-Protein/peptide , 2 types, 12 molecules A
C E G I K B D F H J L
Mass: 2383.698 Da / Num. of mol.: 6 / Fragment: UNP residues 90-110 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P01308
Mass: 3424.967 Da / Num. of mol.: 6 / Fragment: UNP residues 25-54 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P01308
-Non-polymers , 4 types, 217 molecules
|#4: Chemical||#5: Chemical||#6: Water|| ChemComp-HOH / |
|Experiment||Method: X-RAY DIFFRACTION|
|Crystal||Density Matthews: 2.21 Å3/Da / Density % sol: 44.39 %|
|Crystal grow||Temperature: 277 K / Method: vapor diffusion, hanging drop|
Details: sodium citrate, phenol, sodium chloride, zinc acetate, tris
|Diffraction||Mean temperature: 100 K|
|Diffraction source||Source: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.987 Å|
|Detector||Type: ADSC QUANTUM 315r / Detector: CCD / Date: Jun 13, 2012|
|Radiation||Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray|
|Reflection||Resolution: 1.5→42.3 Å / Num. obs: 54128 / % possible obs: 95.8 % / Redundancy: 1.9 % / Net I/σ(I): 13.9|
|Reflection shell||Resolution: 1.5→1.6 Å / Redundancy: 3.5 % / Rmerge(I) obs: 0.84 / Mean I/σ(I) obs: 1.6 / % possible all: 99.3|
|Software||Name: PHENIX / Version: (phenix.refine: 1.9_1692) / Classification: refinement|
|Refinement||Method to determine structure: MOLECULAR REPLACEMENT|
Starting model: 1ZNJ
Resolution: 1.5→42.3 Å / SU ML: 0.17 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 22.37 / Stereochemistry target values: ML
|Solvent computation||Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL|
|Refinement step||Cycle: LAST / Resolution: 1.5→42.3 Å|
|Refine LS restraints|
|LS refinement shell|
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