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Open data
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Basic information
Entry | Database: SASBDB / ID: SASDEW5 |
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![]() | Albumin-insulin detemir 1:6 complex, binding in Südlow's Site II
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Function / homology | ![]() cellular response to calcium ion starvation / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function |
![]() | ![]() 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. |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
-Data source
SASBDB page | ![]() |
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-Related structure data
Related structure data | C: citing same article ( |
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Similar structure data |
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External links
Related items in Molecule of the Month |
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-Models
Model #2456 | ![]() Type: atomic / Symmetry ![]() ![]() |
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Model #2457 | ![]() Type: dummy / Radius of dummy atoms: 2.70 A / Symmetry ![]() ![]() |
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Sample
![]() | Name: Albumin-insulin detemir 1:6 complex, binding in Südlow's Site II Specimen concentration: 8.5 mg/ml / Entity id: 1319 / 1320 |
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Buffer | Name: 6.9 mM Na2HPO4, 11.9 mM m-cresol, 13.7 mM phenol, 157.3 mM glycerol, 38.5 mM NaCl pH: 7.4 |
Entity #1319 | Type: protein / Description: Insulin detemir (Levemir(R), Novo Nordisk A/S) / Formula weight: 5.9 / Num. of mol.: 6 / References: UniProt: P01308 Sequence: GIVEQCCTSI CSLYQLENYC NFVNQHLCGS HLVEALYLVC GERGFFYTPK |
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 |
-Experimental information
Beam | Instrument name: MAX IV I911-4 / City: Lund / 国: Sweden ![]() ![]() | ||||||||||||||||||
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Detector | Name: Pilatus 1M / Type: Dectris / Pixsize x: 172 mm | ||||||||||||||||||
Scan | 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) |
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Result |
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