The crystal structure of insulin

Harding, Marjorie M.; Hodgkin, Dorothy Crowfoot; Kennedy, A.F.; O’Connor, Abby R.; Weitzmann, P.D.J.

doi:10.1016/s0022-2836(66)80274-7

Cited by 86 publications

(31 citation statements)

References 16 publications

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“…For our model investigations insulin from porcine pancreas, BioChemika, ≥85% (GE), ~24 IU/mg was used without further purification. Rhombohedral insulin crystals were grown in non-toxic environment by modifying the conditions used for obtaining Zn-insulin crystals described in [14]. The experimental approach of the cited authors relies on using high NaCl concentrations and alternating addition of HCl and NaOH until obtaining a clear solution with pH = 6.35.…”

Section: Methodsmentioning

confidence: 99%

“…Although the crystals in figure 3 were too small for x-ray investigations it is known from the literature, e.g. [14], that they are built by Zn hexamers. Both temperature dependence of insulin solubility and insulin crystal dissolution were studied using the same thermo-regulated all-glass system (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…5), and primarily on the chloride ions known to be responsible for producing 4Zn or 2Zn rhombohedral insulin crystals (depending on Cl -concentration [14]). The solution flow for the model dissolution experiments was initiated by low hydrostatic under-pressure that was kept constant in time.…”

Section: Methodsmentioning

confidence: 99%

“…The crystal structure of the NaCl-grown rhombohedral Zn-insulin crystals was already reported in [14] and latter refined by Bentley et al [15]. In the rhombohedral insulin crystals there are six insulin molecules per unit cell, which build the known hexamer structure that is interconnected by two or four Zn ions.…”

Section: Introductionmentioning

confidence: 90%

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Growth of rhombohedral insulin crystals and in vitro modeling of their dissolution in the blood stream

Nanev

Dimitrov

Hodzhaoglu

2010

Cryst. Res. Technol.

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Insulin is the only protein that is secreted in a crystalline form in a human healthy body. To mimic the secretion process we used NaCl salting-out to growing tiny rhombohedral Zn-insulin crystals. The dissolution of the insulin crystals is of special interest for the therapeutical praxis, because the human body is supplied with the physiologically active monomers of the insulin through dissolution of the crystalline granules secreted in the pancreatic β-cells. Sets of tiny rhombohedral Zn-insulin crystals, which resembled the granules secreted in the β-cells, were subjected to dissolution in blood plasma and model solutions. The impacts of the solution composition, flow rate, pH and ionic strength on the insulin crystal dissolution were investigated. The effect of the blood plasma was determinant because it dissolved the rhombohedral Zn-insulin crystals almost instantly, while the effects of solution's physicochemical characteristics were of minor importance. In addition, we found that the presence of abundant zinc ions suppressed the dissolution of the insulin crystals.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

See 2 more Smart Citations

Growth of rhombohedral insulin crystals and in vitro modeling of their dissolution in the blood stream

Nanev

Dimitrov

Hodzhaoglu

2010

Cryst. Res. Technol.

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“…Rhombohedral (R3) crystals of porcine insulin grew on 12-mm Teflon-coated metal disks [20] from solutions containing up to 1 mg ml ÿ1 insulin, 0:05M sodium citrate, 0:005M ZnCl 2 , 0% and 15% (v=v) acetone, 0:001M HCl, at pH 7:0 and temperature T 27 C [21]. The solution supersaturation was calculated as C ÿ C e C ÿ1…”

mentioning

confidence: 99%

Stable Equidistant Step Trains during Crystallization of Insulin

2003

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Bunching of growth steps plagues layerwise crystallization of materials in laboratory, industrial, and geological environments, and theory predicts that equidistant step trains are unstable under a variety of conditions. Searching for an example of stable equidistant step trains, we monitored the generation and spatiotemporal evolution of step trains on length scales from 100 nm to 1 mm during the crystallization of insulin, using atomic force microscopy and phase-shifting interferometry. We show that near-equidistant step trains are generated by single and cooperating screw dislocation. The lack of step-step interaction and the overall transport-controlled growth regime further regularize the step train and ensure the stability of the obtained equidistant arrangement.

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A model of insulin fibrils derived from the x-ray crystal structure of a monomeric insulin (despentapeptide insulin)

et al. 1997

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The crystal structure of despentapeptide insulin, a monomeric insulin, has been refined at 1.3 A spacing and subsequently used to predict and model the organization in the insulin fibril. The model makes use of the contacts in the densely packed despentapeptide insulin crystal, and takes into account other experimental evidence, including binding studies with Congo red. The dimensions of this model fibril correspond well with those measured experimentally, and the monomer-monomer contacts within the fibril are in accordance with the known physical chemistry of insulin fibrils. Using this model, it may be possible to predict mutations in insulin that might alleviate problems associated with fibril formation during insulin therapy.

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The crystal structure of insulin

Cited by 86 publications

References 16 publications

Growth of rhombohedral insulin crystals and in vitro modeling of their dissolution in the blood stream

Growth of rhombohedral insulin crystals and in vitro modeling of their dissolution in the blood stream

Stable Equidistant Step Trains during Crystallization of Insulin

A model of insulin fibrils derived from the x-ray crystal structure of a monomeric insulin (despentapeptide insulin)

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