X-ray investigation of gene-engineered human insulin crystallized from a solution containing polysialic acid

Тимофеев, В. И.; Chuprov‐Netochin, Roman N.; Samigina, V. R.; Безуглов, В. В.; Miroshnikov, Konstantin A.; Куранова, И. П.

doi:10.1107/s1744309110000461

Cited by 60 publications

(38 citation statements)

References 17 publications

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“…One can show that rmsd between this structure and PDB structure obtained at pH = 2.1 (PDB ID: 1GUJ) is 0.28 nm. The rmsd between PDB structure obtained at pH = 8.5 [50] (PDB ID: 3I3Z) and the most populated structure is 0.26 nm (Figure S6). Moreover, rmsd between 1GUJ and 3I3Z is about 0.32 nm implying the weak dependence of insulin structure on pH.…”

Section: Resultsmentioning

confidence: 99%

Oligomerization of Peptides LVEALYL and RGFFYT and Their Binding Affinity to Insulin

et al. 2013

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Recently it has been proposed a model for fibrils of human insulin in which the fibril growth proceeds via stacking LVEALYL (fragment 11–17 from chain B of insulin) into pairs of tightly interdigitated -sheets. The experiments have also shown that LVEALYL has high propensity to self-assembly and binding to insulin. This necessitates study of oligomerization of LVEALYL and its binding affinity to full-length insulin. Using the all-atom simulations with Gromos96 43a1 force field and explicit water it is shown that LVEALYL can aggregate. Theoretical estimation of the binding free energy of LVEALYL to insulin by the molecular mechanic Poisson-Boltzmann surface area method reveals its strong binding affinity to chain B, implying that, in agreement with the experiments, LVEALYL can affect insulin aggregation via binding mechanism. We predict that, similar to LVEALYL, peptide RGFFYT (fragment B22-27) can self-assemble and bind to insulin modulating its fibril growth process. The binding affinity of RGFFYT is shown to be comparable with that of LVEALYL.

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Section: Resultsmentioning

confidence: 99%

Oligomerization of Peptides LVEALYL and RGFFYT and Their Binding Affinity to Insulin

et al. 2013

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“…The starting coordinates of B20-30 were taken from the X-ray structure of human insulin (PDB code 3I3Z) [60]. The complex between IDE and the 1-18 portion of the B chain of insulin (PDB code 2WBY) [23] was used for the alignment of B20-30 prior to docking to IDE.…”

Section: Docking Simulationsmentioning

confidence: 99%

Metal ions affect insulin-degrading enzyme activity

Grasso

Salomone

Tundo

et al. 2012

Journal of Inorganic Biochemistry

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Insulin degradation is a finely tuned process that plays a major role in controlling insulin action and most evidence supports IDE (insulin-degrading enzyme) as the primary degradative agent. However, the biomolecular mechanisms involved in the interaction between IDE and its substrates are often obscure, rendering the specific enzyme activity quite difficult to target. On the other hand, biometals, such as copper, aluminum and zinc, have an important role in pathological conditions such as Alzheimer's disease or diabetes mellitus. The metabolic disorders connected with the latter lead to some metallostasis alterations in the human body and many studies point at a high level of interdependence between diabetes and several cations. We have previously reported (Grasso et al., Chem. Eur. J. 17 (2011) 2752-2762) that IDE activity toward Aβ peptides can be modulated by metal ions. Here, we have investigated the effects of different metal ions on the IDE proteolytic activity toward insulin as well as a designed peptide comprising a portion of the insulin B chain (B20-30), which has a very low affinity for metal ions. The results obtained by different experimental techniques clearly show that IDE is irreversibly inhibited by copper(I) but is still able to process its substrates when it is bound to copper(II).

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“…23-25 The three structures are virtually identical. Sequence alignment for the same set of proteins is shown in Figure 1b.…”

Section: Resultsmentioning

confidence: 94%

Examining Protein Surface Structure in Highly Conserved Sequence Variants with Mass Spectrometry

Tao

Julian

2012

Biochemistry

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A simple mass spectrometry based method capable of examining protein structure called SNAPP (selective noncovalent adduct protein probing) is used to evaluate the structural consequences of point mutations in naturally occurring sequence variants from different species. SNAPP monitors changes in the attachment of noncovalent adducts to proteins as a function of structural state. Mutations which lead to perturbations to the electrostatic surface structure of a protein affect noncovalent attachment and are easily observed with SNAPP. Mutations which do not alter the tertiary structure or electrostatic surface structure yield similar results by SNAPP. For example, bovine, porcine, and human insulin all have very similar backbone structures and no basic or acidic residue mutations, and the SNAPP distributions for all three proteins are very similar. In contrast, four variants of cytochrome c (cytc) have varying degrees of sequence homology, which are reflected in the observed SNAPP distributions. Bovine and pigeon cytc have several basic or acidic residue substitutions relative to horse cytc, but the SNAPP distributions for all three proteins are similar. This suggests that these mutations do not significantly influence the protein surface structure. On the other hand, yeast cytc has the least sequence homology and exhibits a unique, though related, SNAPP distribution. Even greater differences are observed for lysozyme. Hen and human lysozyme have identical tertiary structures, but significant variations in the locations of numerous basic and acidic residues. The SNAPP distributions are quite distinct for the two forms of lysozyme, suggesting significant differences in the surface structures. In summary, SNAPP experiments are relatively easy to perform, require minimal sample consumption, and provide a facile route for comparison of protein surface structure between highly homologous proteins.

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X-ray investigation of gene-engineered human insulin crystallized from a solution containing polysialic acid

Cited by 60 publications

References 17 publications

Oligomerization of Peptides LVEALYL and RGFFYT and Their Binding Affinity to Insulin

Oligomerization of Peptides LVEALYL and RGFFYT and Their Binding Affinity to Insulin

Metal ions affect insulin-degrading enzyme activity

Examining Protein Surface Structure in Highly Conserved Sequence Variants with Mass Spectrometry

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