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Yorodumi- SASDEZ5: Albumin-insulin detemir 2:12 complex, P2 symmetry (Human Albumin ... -
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-Basic information
Entry | Database: SASBDB / ID: SASDEZ5 |
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Sample | Albumin-insulin detemir 2:12 complex, P2 symmetry
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Function / homology | Function and homology information cellular response to calcium ion starvation / exogenous protein binding / Ciprofloxacin ADME / enterobactin binding / Heme biosynthesis / HDL remodeling / negative regulation of mitochondrial depolarization / Prednisone ADME / Heme degradation / negative regulation of NAD(P)H oxidase activity ...cellular response to calcium ion starvation / exogenous protein binding / Ciprofloxacin ADME / enterobactin binding / Heme biosynthesis / HDL remodeling / negative regulation of mitochondrial depolarization / Prednisone ADME / Heme degradation / 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 / Aspirin ADME / regulation of protein secretion / positive regulation of peptide hormone secretion / positive regulation of respiratory burst / negative regulation of acute inflammatory response / antioxidant activity / 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 / toxic substance binding / 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 / Scavenging of heme from plasma / 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 / Recycling of bile acids and salts / 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 / cellular response to starvation / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of glycolytic process / positive regulation of mitotic nuclear division / Insulin receptor signalling cascade / platelet alpha granule lumen / 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 / fatty acid binding / positive regulation of glucose import / positive regulation of protein secretion / negative regulation of proteolysis / positive regulation of cell differentiation / Post-translational protein phosphorylation / regulation of transmembrane transporter activity / insulin receptor binding / wound healing / regulation of synaptic plasticity / vasodilation / hormone activity / Cytoprotection by HMOX1 / cognition / positive regulation of neuron projection development / positive regulation of protein localization to nucleus / Golgi lumen / glucose metabolic process / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / regulation of protein localization / glucose homeostasis / pyridoxal phosphate binding / Platelet degranulation / 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 / protein-folding chaperone binding / protease binding / secretory granule lumen / positive regulation of MAPK cascade Similarity search - Function |
Citation | Journal: Acta Crystallogr D Struct Biol / Year: 2019 Title: Solution structures of long-acting insulin analogues and their complexes with albumin. Authors: Line A Ryberg / Pernille Sønderby / Fabian Barrientos / Jens T Bukrinski / Günther H J Peters / Pernille Harris / Abstract: The lipidation of peptide drugs is one strategy to obtain extended half-lives, enabling once-daily or even less frequent injections for patients. The half-life extension results from a combination of ...The lipidation of peptide drugs is one strategy to obtain extended half-lives, enabling once-daily or even less frequent injections for patients. The half-life extension results from a combination of self-association and association with human serum albumin (albumin). The self-association and association with albumin of two insulin analogues, insulin detemir and insulin degludec, were investigated by small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS) in phenolic buffers. Detemir shows concentration-dependent self-association, with an equilibrium between hexamer, dihexamer, trihexamer and larger species, while degludec appears as a dihexamer independent of concentration. The solution structure of the detemir trihexamer has a bent shape. The stoichiometry of the association with albumin was studied using DLS. For albumin-detemir the molar stoichiometry was determined to be 1:6 (albumin:detemir ratio) and for albumin-degludec it was between 1:6 and 1:12 (albumin:degludec ratio). Batch SAXS measurements of a 1:6 albumin:detemir concentration series revealed a concentration dependence of complex formation. The data allowed the modelling of a complex between albumin and a detemir hexamer and a complex consisting of two albumins binding to opposite ends of a detemir dihexamer. Measurements of size-exclusion chromatography coupled to SAXS revealed a complex between a degludec dihexamer and albumin. Based on the results, equilibria for the albumin-detemir and albumin-degludec mixtures are proposed. |
Contact author |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Data source
SASBDB page | SASDEZ5 |
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-Related structure data
Related structure data | C: citing same article (ref.) |
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Similar structure data |
-External links
Related items in Molecule of the Month |
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-Models
Model #2465 | Type: atomic / Chi-square value: 1.115 / P-value: 0.000021 Search similar-shape structures of this assembly by Omokage search (details) |
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Model #2467 | Type: dummy / Radius of dummy atoms: 4.20 A / Chi-square value: 0.887 / P-value: 0.000107 Search similar-shape structures of this assembly by Omokage search (details) |
-Sample
Sample | Name: Albumin-insulin detemir 2:12 complex, P2 symmetry / Specimen concentration: 15.6 mg/ml / Entity id: 1320 / 1321 |
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Buffer | Name: 8.8 mM Na2HPO4, 10.6 mM m-cresol, 12.2 mM phenol, 140.9 mM glycerol, 56.9 mM NaCl pH: 7.4 |
Entity #1320 | Type: protein Description: Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.) Formula weight: 66.472 / Num. of mol.: 1 / References: UniProt: P02768 Sequence: DAHKSEVAHR FKDLGEENFK ALVLIAFAQY LQQCPFEDHV KLVNEVTEFA KTCVADESAE NCDKSLHTLF GDKLCTVATL RETYGEMADC CAKQEPERNE CFLQHKDDNP NLPRLVRPEV DVMCTAFHDN EETFLKKYLY EIARRHPYFY APELLFFAKR YKAAFTECCQ ...Sequence: DAHKSEVAHR FKDLGEENFK ALVLIAFAQY LQQCPFEDHV KLVNEVTEFA KTCVADESAE NCDKSLHTLF GDKLCTVATL RETYGEMADC CAKQEPERNE CFLQHKDDNP NLPRLVRPEV DVMCTAFHDN EETFLKKYLY EIARRHPYFY APELLFFAKR YKAAFTECCQ AADKAACLLP KLDELRDEGK ASSAKQRLKC ASLQKFGERA FKAWAVARLS QRFPKAEFAE VSKLVTDLTK VHTECCHGDL LECADDRADL AKYICENQDS ISSKLKECCE KPLLEKSHCI AEVENDEMPA DLPSLAADFV ESKDVCKNYA EAKDVFLGMF LYEYARRHPD YSVVLLLRLA KTYETTLEKC CAAADPHECY AKVFDEFKPL VEEPQNLIKQ NCELFEQLGE YKFQNALLVR YTKKVPQVST PTLVEVSRNL GKVGSKCCKH PEAKRMPCAE DYLSVVLNQL CVLHEKTPVS DRVTKCCTES LVNRRPCFSA LEVDETYVPK EFNAETFTFH ADICTLSEKE RQIKKQTALV ELVKHKPKAT KEQLKAVMDD FAAFVEKCCK ADDKETCFAE EGKKLVAASQ AALGL |
Entity #1321 | Type: protein / Description: Insulin detemir (Levemir(R), Novo Nordisk A/S) / Formula weight: 5.9 / Num. of mol.: 12 / References: UniProt: P01308 Sequence: GIVEQCCTSI CSLYQLENYC NFVNQHLCGS HLVEALYLVC GERGFFYTPK |
-Experimental information
Beam | Instrument name: MAX IV I911-4 / City: Lund / 国: Sweden / Type of source: X-ray synchrotron / Wavelength: 0.091 Å / Dist. spec. to detc.: 1.962 mm | ||||||||||||||||||
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Detector | Name: Pilatus 1M / Type: Dectris / Pixsize x: 172 mm | ||||||||||||||||||
Scan | Title: Albumin-insulin detemir 2:12 complex, P2 symmetry / Measurement date: Sep 25, 2015 / Cell temperature: 20 °C / Exposure time: 30 sec. / Number of frames: 4 / Unit: 1/nm /
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Distance distribution function P(R) | Sofotware P(R): GNOM 5.0 / Number of points: 243 /
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Result | D max: 19.5 / Type of curve: single_conc /
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