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Role of B13 Glu in insulin assembly. The hexamer structure of recombinant mutant (B13 Glu-->Gln) insulin.

Bentley GA, Brange J, Derewenda Z, Dodson EJ, Dodson GG, Markussen J, Wilkinson AJ, Wollmer A, Xiao B
J Mol Biol 228 1163-76 (1992)
Cited: 22 times
EuropePMC logo PMID: 1361949

Abstract

The assembly of the insulin hexamer brings the six B13 glutamate side-chains at the centre into close proximity. Their mutual repulsion is unfavourable and zinc co-ordination to B10 histidine is necessary to stabilize the well known zinc-containing hexamers. Since B13 is always a carboxylic acid in all known sequences of hexamer forming insulins, it is likely to be important in the hormone's biology. The mutation of B13 Glu-->Gln leads to a stable zinc-free hexamer with somewhat reduced potency. The structures of the zinc-free B13 Gln hexamer and the 2Zn B13 insulin hexamer have been determined by X-ray analysis and refined with 2.5 A and 2.0 A diffraction data, respectively. Comparisons show that in 2Zn B13 Gln insulin, the hexamer structure (T6) is very like that of the native hormone. On the other hand, the zinc-free hexamer assumes a quaternary structure (T3/R3) seen in the native 4Zn insulin hexamer, and normally associated only with high chloride ion concentrations in the medium. The crystal structures show the B13 Gln side-chains only contact water in contrast to the B13 glutamate in 2Zn insulin. The solvation of the B13 Gln may be associated with this residue favouring helix at B1 to B8. The low potency of the B13 Gln insulin also suggests the residue influences the hormone's conformation.

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  1. The role of assembly in insulin's biosynthesis. Dodson G, Steiner D. Curr. Opin. Struct. Biol. 8 189-194 (1998)
  2. Understanding insulin and its receptor from their three-dimensional structures. Lawrence MC. Mol Metab 52 101255 (2021)
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  1. Insulin analogs with improved pharmacokinetic profiles. Brange J, Vølund A. Adv. Drug Deliv. Rev. 35 307-335 (1999)
  2. Binding of phenol to R6 insulin hexamers. Berchtold H, Hilgenfeld R. Biopolymers 51 165-172 (1999)
  3. Protein flexibility: multiple molecular dynamics simulations of insulin chain B. Legge FS, Budi A, Treutlein H, Yarovsky I. Biophys. Chem. 119 146-157 (2006)
  4. Application of SIMSTEX to oligomerization of insulin analogs and mutants. Chitta RK, Rempel DL, Grayson MA, Remsen EE, Gross ML. J. Am. Soc. Mass Spectrom. 17 1526-1534 (2006)
  5. Spectroscopic evidence for preexisting T- and R-state insulin hexamer conformations. Choi WE, Borchardt D, Kaarsholm NC, Brzovic PS, Dunn MF. Proteins 26 377-390 (1996)
  6. Relationship between self-association of insulin and its secretion efficiency in yeast. Kjeldsen T, Pettersson AF. Protein Expr. Purif. 27 331-337 (2003)
  7. 3D deep convolutional neural networks for amino acid environment similarity analysis. Torng W, Altman RB. BMC Bioinformatics 18 302 (2017)
  8. Crystallographic characterization of two novel crystal forms of human insulin induced by chaotropic agents and a shift in pH. Norrman M, Schluckebier G. BMC Struct. Biol. 7 83 (2007)
  9. Enhancing the T-->R transition of insulin by helix-promoting sequence modifications at the N-terminal B-chain. Shneine J, Voswinkel M, Federwisch M, Wollmer A. Biol. Chem. 381 127-133 (2000)
  10. Structural signatures of the complex formed between 3-nitro-4-hydroxybenzoate and the Zn(II)-substituted R(6) insulin hexamer. Olsen HB, Leuenberger-Fisher MR, Kadima W, Borchardt D, Kaarsholm NC, Dunn MF. Protein Sci. 12 1902-1913 (2003)
  11. An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein. Glidden MD, Aldabbagh K, Phillips NB, Carr K, Chen YS, Whittaker J, Phillips M, Wickramasinghe NP, Rege N, Swain M, Peng Y, Yang Y, Lawrence MC, Yee VC, Ismail-Beigi F, Weiss MA. J. Biol. Chem. 293 47-68 (2018)
  12. Equilibrium Ensembles for Insulin Folding from Bias-Exchange Metadynamics. Singh R, Bansal R, Rathore AS, Goel G. Biophys. J. 112 1571-1585 (2017)
  13. Packing defects functionalize soluble proteins. Fernández A. FEBS Lett. 589 967-973 (2015)
  14. Kinetics of Phenol Escape from the Insulin R6 Hexamer. Antoszewski A, Lorpaiboon C, Strahan J, Dinner AR. J Phys Chem B 125 11637-11649 (2021)
  15. Structure-based stabilization of insulin as a therapeutic protein assembly via enhanced aromatic-aromatic interactions. Rege NK, Wickramasinghe NP, Tustan AN, Phillips NFB, Yee VC, Ismail-Beigi F, Weiss MA. J. Biol. Chem. 293 10895-10910 (2018)
  16. The T2 structure of polycrystalline cubic human insulin. Triandafillidis DP, Karavassili F, Spiliopoulou M, Valmas A, Athanasiadou M, Nikolaras G, Fili S, Kontou P, Bowler MW, Chasapis CT, Von Dreele RB, Fitch AN, Margiolaki I. Acta Crystallogr D Struct Biol 79 374-386 (2023)


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