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Yorodumi- PDB-3kq6: Enhancing the Therapeutic Properties of a Protein by a Designed Z... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3kq6 | ||||||
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Title | Enhancing the Therapeutic Properties of a Protein by a Designed Zinc-Binding Site, Structural principles of a novel long-acting insulin analog | ||||||
Components |
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Keywords | HORMONE / zinc-binding site / long-acting insulin analog / receptor binding / Carbohydrate metabolism / Cleavage on pair of basic residues / Diabetes mellitus / Disease mutation / Disulfide bond / Glucose metabolism / Pharmaceutical / Secreted | ||||||
Function / homology | Function and homology information negative regulation of NAD(P)H oxidase activity / 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 / Insulin processing / regulation of protein secretion / positive regulation of peptide hormone secretion ...negative regulation of NAD(P)H oxidase activity / 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 / Insulin processing / regulation of protein secretion / 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 / regulation of cellular amino acid metabolic process / 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 / regulation of protein localization to plasma membrane / fatty acid homeostasis / Signal attenuation / negative regulation of lipid catabolic process / negative regulation of gluconeogenesis / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / COPI-mediated anterograde transport / positive regulation of lipid biosynthetic process / negative regulation of reactive oxygen species biosynthetic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / positive regulation of insulin receptor signaling pathway / nitric oxide-cGMP-mediated signaling / 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 / activation of protein kinase B activity / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of glycolytic process / positive regulation of mitotic nuclear division / Insulin receptor signalling cascade / positive regulation of nitric-oxide synthase activity / positive regulation of cytokine production / positive regulation of long-term synaptic potentiation / acute-phase response / Regulation of insulin secretion / negative regulation of protein catabolic process / endosome lumen / positive regulation of glucose import / positive regulation of protein secretion / negative regulation of proteolysis / positive regulation of cell differentiation / regulation of transmembrane transporter activity / insulin receptor binding / wound healing / regulation of synaptic plasticity / vasodilation / hormone activity / cognition / positive regulation of neuron projection development / positive regulation of protein localization to nucleus / Golgi lumen / glucose metabolic process / regulation of protein localization / glucose homeostasis / insulin receptor signaling pathway / cell-cell signaling / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / positive regulation of NF-kappaB transcription factor activity / positive regulation of cell growth / protease binding / secretory granule lumen / 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 / Golgi membrane / endoplasmic reticulum lumen / 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 | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å | ||||||
Authors | Wan, Z.L. / Hu, S.Q. / Whittaker, L. / Phillips, N.B. / Whittake, J. / Ismail-Beigi, F. / Weiss, M.A. | ||||||
Citation | Journal: J.Biol.Chem. / Year: 2010 Title: Supramolecular protein engineering: design of zinc-stapled insulin hexamers as a long acting depot. Authors: Phillips, N.B. / Wan, Z.L. / Whittaker, L. / Hu, S.Q. / Huang, K. / Hua, Q.X. / Whittaker, J. / Ismail-Beigi, F. / Weiss, M.A. #1: Journal: Biochemistry / Year: 2004 Title: Enhancing the activity of insulin at the receptor interface: crystal structure and photo-cross-linking of A8 analogues. Authors: Wan, Z.L. / Xu, B. / Chu, Y.C. / Li, B. / Nakagawa, S.H. / Qu, Y. / Hu, S.Q. / Katsoyannis, P.G. / Weiss, M.A. #2: Journal: Philos.Trans.R.Soc.London,Ser.B / Year: 1988 Title: The structure of 2zn pig insulin crystal at 1.5 A resolution Authors: Baker, E.N. / Blundell, T.L. / Cutfield, J.F. / Cutfield, S.M. / Dodson, E.J. / Dodson, G.G. / Hodgkin, D. / Isaacs, N.W. / Reynolds, C.D. #3: Journal: Nature / Year: 1976 Title: Structure of insulin in 4-zinc insulin Authors: Bentley, G. / Dodson, E. / Dodson, G. / Hodgkin, D. / Mercola, D. #4: Journal: Nature / Year: 1989 Title: Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer Authors: Derewenda, U. / Derewenda, Z. / Dodson, E. / Dodson, G. / Reynold, C. / Smith, G. / Sparks, C. / Swenson, D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3kq6.cif.gz | 35.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3kq6.ent.gz | 24.2 KB | Display | PDB format |
PDBx/mmJSON format | 3kq6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3kq6_validation.pdf.gz | 449.3 KB | Display | wwPDB validaton report |
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Full document | 3kq6_full_validation.pdf.gz | 450.6 KB | Display | |
Data in XML | 3kq6_validation.xml.gz | 7.8 KB | Display | |
Data in CIF | 3kq6_validation.cif.gz | 9.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kq/3kq6 ftp://data.pdbj.org/pub/pdb/validation_reports/kq/3kq6 | HTTPS FTP |
-Related structure data
Related structure data | 1rweS S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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Components on special symmetry positions |
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-Components
-Protein/peptide , 2 types, 4 molecules ACBD
#1: Protein/peptide | Mass: 2429.774 Da / Num. of mol.: 2 / Mutation: E4H, T4H / Source method: obtained synthetically / Details: biosynthetic peptide / Source: (synth.) Homo sapiens (human) / References: UniProt: P01308 #2: Protein/peptide | Mass: 3433.953 Da / Num. of mol.: 2 / Source method: obtained synthetically / Details: biosynthetic peptide / Source: (synth.) Homo sapiens (human) / References: UniProt: P01308 |
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-Non-polymers , 4 types, 88 molecules
#3: Chemical | #4: Chemical | #5: Chemical | ChemComp-IPH / | #6: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 1.82 Å3/Da / Density % sol: 32.46 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion / pH: 8 Details: 0.02 M Tris, 0.05 M sodium citrate, 5% acetone, 0.03% phenol, 0.01% zinc acetate, pH 8.0, VAPOR DIFFUSION, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 4.2.2 / Wavelength: 1.0000,1.2398 | |||||||||
Detector | Type: NOIR-1 / Detector: CCD / Date: Nov 4, 2005 / Details: Double crystal | |||||||||
Radiation | Monochromator: Double crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||
Radiation wavelength |
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Reflection | Resolution: 1.9→32.05 Å / Num. all: 6520 / Num. obs: 6488 / % possible obs: 99.5 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 5.49 % / Biso Wilson estimate: 27.7 Å2 / Rmerge(I) obs: 0.057 / Net I/σ(I): 14.1 | |||||||||
Reflection shell | Resolution: 1.9→1.97 Å / Redundancy: 5.43 % / Rmerge(I) obs: 0.422 / Mean I/σ(I) obs: 3 / Num. unique all: 658 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 1RWE Resolution: 1.9→32.05 Å / Isotropic thermal model: restrained / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / Stereochemistry target values: Engh & Huber
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Displacement parameters | Biso mean: 43.3 Å2
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Refine analyze | Luzzati coordinate error obs: 0.27 Å / Luzzati d res low obs: 5 Å / Luzzati sigma a obs: 0.23 Å | |||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.9→32.05 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.9→2.02 Å / Rfactor Rfree error: 0.035
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