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The structure of a complex of hexameric insulin and 4'-hydroxyacetanilide.

Smith GD, Ciszak E
Proc Natl Acad Sci U S A 91 8851-5 (1994)
Related entries: 1trz, 1tym

Cited: 26 times
EuropePMC logo PMID: 8090735

Abstract

X-ray crystallographic studies have been carried out on human insulin crystals grown in the presence of 4'-hydroxyacetanilide (Tylenol) and show that this nontoxic phenolic derivative can induce the T-->R transition, producing a T3R3 hexamer. Two different crystals, grown under different conditions, are rhombohedral, space group R3, with cell constants a = 81.11, c = 37.97 and a = 80.88, c = 37.60 A. The T3R3 hexamer is symmetric, resulting from the presence of a crystallographic threefold axis, and the asymmetric unit consists of a TR dimer. Data to a resolution of 1.9 A were measured on a crystal from each of the two crystallizations and the structures have been refined to residuals of 0.168 and 0.173. The guest molecule is bound by the R-state monomer through the formation of two hydrogen bonds from the hydroxy group of Tylenol to the carbonyl oxygen and the nitrogen of A6 Cys and A11 Cys, respectively. Due to steric constraints of the phenolic binding site, the acetamide group of Tylenol is rotated approximately 50 degrees out of the plane of the phenyl group and the methyl group is cis; no hydrogen bonds exist between the acetamide group and the hexamer. Although the zinc ion, which is bound to the R-state trimer, has tetrahedral coordination in both structures, the T-state zinc is observed to have octahedral coordination in one structure but tetrahedral coordination in the other. The side chain of A10 Ile in the R-state monomer adopts a high-energy conformation as a result of close contact to a residue in an adjacent dimer and may explain in part the differences between therapeutic preparations of beef insulin, for which A10 is a Val residue, and human insulin.

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  2. A divergent INS protein in Caenorhabditis elegans structurally resembles human insulin and activates the human insulin receptor. Hua QX, Nakagawa SH, Wilken J, Ramos RR, Jia W, Bass J, Weiss MA. Genes Dev. 17 826-831 (2003)
  3. Enhancing the activity of a protein by stereospecific unfolding: conformational life cycle of insulin and its evolutionary origins. Hua QX, Xu B, Huang K, Hu SQ, Nakagawa S, Jia W, Wang S, Whittaker J, Katsoyannis PG, Weiss MA. J. Biol. Chem. 284 14586-14596 (2009)
  4. An Achilles' heel in an amyloidogenic protein and its repair: insulin fibrillation and therapeutic design. Yang Y, Petkova A, Huang K, Xu B, Hua QX, Ye IJ, Chu YC, Hu SQ, Phillips NB, Whittaker J, Ismail-Beigi F, Mackin RB, Katsoyannis PG, Tycko R, Weiss MA. J. Biol. Chem. 285 10806-10821 (2010)
  5. Crystal structure of a "nonfoldable" insulin: impaired folding efficiency despite native activity. Liu M, Wan ZL, Chu YC, Aladdin H, Klaproth B, Choquette M, Hua QX, Mackin RB, Rao JS, De Meyts P, Katsoyannis PG, Arvan P, Weiss MA. J. Biol. Chem. 284 35259-35272 (2009)
  6. Contribution of TyrB26 to the Function and Stability of Insulin: STRUCTURE-ACTIVITY RELATIONSHIPS AT A CONSERVED HORMONE-RECEPTOR INTERFACE. Pandyarajan V, Phillips NB, Rege N, Lawrence MC, Whittaker J, Weiss MA. J. Biol. Chem. 291 12978-12990 (2016)
  7. Identified the Synergistic Mechanism of Drynariae Rhizoma for Treating Fracture Based on Network Pharmacology. Lin H, Wang X, Wang L, Dong H, Huang P, Cai Q, Mo Y, Huang F, Jiang Z. Evid Based Complement Alternat Med 2019 7342635 (2019)
  8. Deciphering the hidden informational content of protein sequences: foldability of proinsulin hinges on a flexible arm that is dispensable in the mature hormone. Liu M, Hua QX, Hu SQ, Jia W, Yang Y, Saith SE, Whittaker J, Arvan P, Weiss MA. J. Biol. Chem. 285 30989-31001 (2010)
  9. The structure and function of insulin: decoding the TR transition. Weiss MA. Vitam. Horm. 80 33-49 (2009)
  10. An Efficient Method to Evaluate Intermolecular Interaction Energies in Large Systems Using Overlapping Multicenter ONIOM and the Fragment Molecular Orbital Method. Asada N, Fedorov DG, Kitaura K, Nakanishi I, Merz KM. J Phys Chem Lett 3 2604-2610 (2012)
  11. Conformational dynamics of insulin. Hua QX, Jia W, Weiss MA. Front Endocrinol (Lausanne) 2 48 (2011)
  12. Extending Halogen-based Medicinal Chemistry to Proteins: IODO-INSULIN AS A CASE STUDY. El Hage K, Pandyarajan V, Phillips NB, Smith BJ, Menting JG, Whittaker J, Lawrence MC, Meuwly M, Weiss MA. J. Biol. Chem. 291 27023-27041 (2016)
  13. Computational and structural evidence for neurotransmitter-mediated modulation of the oligomeric states of human insulin in storage granules. Palivec V, Viola CM, Kozak M, Ganderton TR, Křížková K, Turkenburg JP, Halušková P, Žáková L, Jiráček J, Jungwirth P, Brzozowski AM. J. Biol. Chem. 292 8342-8355 (2017)
  14. PMFF: Development of a Physics-Based Molecular Force Field for Protein Simulation and Ligand Docking. Hwang SB, Lee CJ, Lee S, Ma S, Kang YM, Cho KH, Kim SY, Kwon OY, Yoon CN, Kang YK, Yoon JH, Nam KY, Kim SG, In Y, Chai HH, Acree WE, Grant JA, Gibson KD, Jhon MS, Scheraga HA, No KT. J Phys Chem B 124 974-989 (2020)


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  2. Amyloid Fibrillation of Insulin: Amelioration Strategies and Implications for Translation. Fagihi MHA, Bhattacharjee S. ACS Pharmacol Transl Sci 5 1050-1061 (2022)

Articles citing this publication (10)

  1. Role of C-terminal B-chain residues in insulin assembly: the structure of hexameric LysB28ProB29-human insulin. Ciszak E, Beals JM, Frank BH, Baker JC, Carter ND, Smith GD. Structure 3 615-622 (1995)
  2. Physicochemical basis for the rapid time-action of LysB28ProB29-insulin: dissociation of a protein-ligand complex. Bakaysa DL, Radziuk J, Havel HA, Brader ML, Li S, Dodd SW, Beals JM, Pekar AH, Brems DN. Protein Sci. 5 2521-2531 (1996)
  3. Mini-proinsulin and mini-IGF-I: homologous protein sequences encoding non-homologous structures. Hua QX, Hu SQ, Jia W, Chu YC, Burke GT, Wang SH, Wang RY, Katsoyannis PG, Weiss MA. J. Mol. Biol. 277 103-118 (1998)
  4. Assembly and dissociation of human insulin and LysB28ProB29-insulin hexamers: a comparison study. Birnbaum DT, Kilcomons MA, DeFelippis MR, Beals JM. Pharm. Res. 14 25-36 (1997)
  5. Atomic force microscopy of insulin single crystals: direct visualization of molecules and crystal growth. Yip CM, Ward MD. Biophys. J. 71 1071-1078 (1996)
  6. Binding of phenol to R6 insulin hexamers. Berchtold H, Hilgenfeld R. Biopolymers 51 165-172 (1999)
  7. A novel complex of a phenolic derivative with insulin: structural features related to the T-->R transition. Smith GD, Ciszak E, Pangborn W. Protein Sci. 5 1502-1511 (1996)
  8. Ligand perturbation effects on a pseudotetrahedral Co(II)(His)3-ligand site. A magnetic circular dichroism study of the Co(II)-substituted insulin hexamer. Brader ML, Kaarsholm NC, Harnung SE, Dunn MF. J. Biol. Chem. 272 1088-1094 (1997)
  9. Preparation of a microcrystalline suspension formulation of Lys(B28)Pro(B29)-human insulin with ultralente properties. Richards JP, Stickelmeyer MP, Frank BH, Pye S, Barbeau M, Radziuk J, Smith GD, DeFelippis MR. J Pharm Sci 88 861-867 (1999)
  10. Equilibrium Ensembles for Insulin Folding from Bias-Exchange Metadynamics. Singh R, Bansal R, Rathore AS, Goel G. Biophys. J. 112 1571-1585 (2017)


Related citations provided by authors (2)

  1. Crystallographic evidence for dual coordination around zinc in the T3R3 human insulin hexamer.. Ciszak E, Smith GD Biochemistry 33 1512-7 (1994)
  2. Structural stability in the 4-zinc human insulin hexamer.. Smith GD, Swenson DC, Dodson EJ, Dodson GG, Reynolds CD Proc Natl Acad Sci U S A 81 7093-7 (1984)

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