Sunday, January 4, 2015

The insulin structure and flexibility macromolecules Insulin is a 5.8 kDa peptide hormone. In the c

Insulin macromolecules flexibility and bioactivity
Biological macromolecules macromolecules structure normally macromolecules presented macromolecules as a static image. However, it is well known that the molecules are flexible and in constant internal motion. The frequency of these movements extending macromolecules from the rapid vibrations macromolecules of covalent bonds on the picosecond scale, to slow reorienteringer of major parts of the molecule, which extend macromolecules over hours or weeks. macromolecules It is becoming increasingly clear that this flexibility and movement of biomakromolekylerne is important for their function. Recently published NMR studies [1,2] thus shows a clear correlation between a protein's activity and movement of the areas of the protein molecule which are essential for its activity. macromolecules
The insulin structure and flexibility macromolecules Insulin is a 5.8 kDa peptide hormone. In the crystal phase has the naturally occurring insulin (the native insulin), macromolecules a structure as shown in Figure 1. In aqueous solution, in which it performs its function, form the insulin molecule, depending on the physical macromolecules conditions it is located below, various types of units with varying degrees of flexibility. Also mutations affecting the structure and flexibility of the insulin molecule to different degrees. One of the most stable and solid forms of the insulin is obtained in the presence of Zn2 + ions and phenol. Here are formed in aqueous solution has a hexamer comprising six insulin macromolecules molecules that assume all the so-called R-type [3], which is shown in Figure 2. In the R-form is the existing B kædehelix (B9-B19) extended to also include the N-terminal end of the chain, i.e., the amino acid residues B1-B8. T-form, which is the normal structure of insulin (Figure 1), also forms a hexamer in the presence of Zn2 + ions. T6 hexamer is, however, considerably less stable than the R6 hexamer, and it has not been possible to make an accurate determination of its structure macromolecules in solution. Insulinmutanters flexibility alternative to the relatively fixed structure of the dimeric SerB9Asp macromolecules mutant [4], in which Serine at position B9 is replaced with Aspartic acid, and the monomer addition, [PheB25] mutant [5], wherein the phenylalanine at position B25 has been removed, of partially unfolded mutants as CysA6Ser, CysA11Ser insulin macromolecules [6], CysA6Ala, CysA11Ala insulin [7] and PheB24Gly insulin [8], to the highly flexible mutant ThrB27Pro, ProB28Thr insulin (insulin PT) [9]. The biologically active form of insulin macromolecules is the monomer. However, it has long been known that the structure of the insulin monomer has the crystal phase and stored in the organism (figure 1) is the active form [10]. Insulin molecule must therefore undergo conformational changes to be able to bind to the insulin receptor and thus exert its glucose-lowering effect. In order to clarify how the binding of insulin molecule takes place, has in recent years research mainly focused on specific areas of the insulin macromolecules molecule. It is along this road has become possible to gain insight macromolecules into which parts of the molecule involved in receptor binding.
Insulin interaction with the insulin receptor, insulin receptor (IR) is a 480 kDa membrane protein that consists of four polypeptide chains: two alpha chains and two b-chains. Insulin binds to the a-chains of the extracellular domain. The structure of this domain is unknown, as is the structure of the receptor-bound macromolecules form of insulin has not yet been solved. The mechanism by which the binding macromolecules to the receptor takes place and the structure of the receptor binding insulin molecule can therefore so far examined only indirectly by studying insulinmutanter with varying structures and correlate structural differences with the biological activity. Using. point mutations and chemical modifications, it has been possible to determine which of the insulin amino acid residues required for binding to the receptor. In particular, residues in the AI-helix and TyrA19, and in the B helix and the C-terminal end of the B chain, which is important macromolecules in this context macromolecules [11-14]. X-ray crystallographic studies of B29-A1 peptide bottom insulin mutant indicated that the mutant has the same secondary and tertiary structure macromolecules as the native insulin [10]. It was also found that the mutant is inactive. These results macromolecules show that flexibility is paramount to insulin's ability to express its biological activity. NMR studies of a second insulin mutant, the active PheB24Gly insulin [8], wherein the C-terminal macromolecules end of the B chain is rotated away, and is completely separated from the rest of the molecule, suggesting that such a movement is required, the IR to connect with the amino acid residues in the insulin molecule, which interacts with the insulin receptor IR-complex. On the C-terminal end of the B chain flips out, as for PheB24Gly insulin, or simply scroll to side, as has been suggested based on structural studies of TyrB16Glu, PheB24Gly, des-B30-insulin [15], lacking yet to be determined.
A chain importance A-chain importance of receptor interaction has been extensively studied. Especially IleA2 and ValA3 are important in this regard, by replacing these residues resulte

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