User:David L. Nelson/Sandbox 9: Difference between revisions
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<Structure load='1APH' size='400' frame='true' align='right' caption='human insulin dimer ([[1APH]])' scene='User:David_L._Nelson/Sandbox_9/Main/1'/> | <Structure load='1APH' size='400' frame='true' align='right' caption='human insulin dimer ([[1APH]])' scene='User:David_L._Nelson/Sandbox_9/Main/1'/> | ||
The primary structure of the insulin protein is relatively simple, consisting of only two chains of amino acids. The two chains, the <scene name='User:David_L._Nelson/Sandbox_9/A_chain/1'>A-Chain</scene> and the <scene name='User:David_L._Nelson/Sandbox_9/B_chain/1'>B-Chain</scene> have 21 and 30 amino acids respectively. The A-Chain has a free amine group on the N-terminal and a free carboxylic acid on the C-terminal, both of which become important in the binding of the protein. The amino acids are termed residues, which refers to the loss of a hydrogen atom from the peptide bonding in order to form the polymer. | |||
The secondary structure is fairly compact. At this level, we begin to see the <scene name='User:David_L._Nelson/Sandbox_9/Helix/1'>alpha helices</scene>. The A-chain contains two sections of alpha helixes in the A-chain between Isoleucine (A2) and Threonine (A8) as well as Leucine (A13) and Tyrosine (A19). These two sections are important, in that they allow they are able to lie alongside each other in Van der Waals contact. These residues are highly conserved evolutionarily, and are vital in the structure and function of the insulin hormone. | |||
A Van der Waals force is different than a covalent and ionic bond, and can be important in structural biology in that it helps to define the solubility of organic compounds. The B-chain also contains an alpha helix, which is larger than those in the A-chain. The alpha helix in the B-chain runs from B9 to B19. It also folds into somewhat of a ‘U’ shape by the glycine residues at B20 and B23. This shape allows the C-terminal residues, Phenylalanine (B24) and Tyrosine (B26), to also be in Van der Waals contact with the alpha helix. This becomes important in the binding of the insulin protein to the insulin receptor. The B-chain’s highly conserved, and thus crucial region ranges from B8-25. | |||
The tertiary structure contains <scene name='User:David_L._Nelson/Sandbox_9/Main/2'>three disulfide bonds</scene> that, along with the Van der Waal’s forces, stabilize the molecule. This disulfide bonds are highlighted in red. The disulfide bonds are formed between cysteines. There are <scene name='User:David_L._Nelson/Sandbox_9/Main/3'>six cyestines</scene>, highlighted in blue, with four in the A-chain (A6,A7,A11,A20), and 2 in the B-chain (B7,B19). More specifically these bonds are formed between A6 and A11, A7 and B7, and A20 and B19. These become very important in receptor binding for insulin. | The tertiary structure contains <scene name='User:David_L._Nelson/Sandbox_9/Main/2'>three disulfide bonds</scene> that, along with the Van der Waal’s forces, stabilize the molecule. This disulfide bonds are highlighted in red. The disulfide bonds are formed between cysteines. There are <scene name='User:David_L._Nelson/Sandbox_9/Main/3'>six cyestines</scene>, highlighted in blue, with four in the A-chain (A6,A7,A11,A20), and 2 in the B-chain (B7,B19). More specifically these bonds are formed between A6 and A11, A7 and B7, and A20 and B19. These become very important in receptor binding for insulin. | ||
These cysteine residues promote a parallel arrangement between A7-20 and B7-19, and more specifically the A6-A11 disulfide bond brings the C-terminal TyrA19 and the N-terminal GlyA1, IleA2, ValA3 closer together. Furthermore, the B-chain C-terminal of LeuB24, TyrB25, LeuB26 is brought near the A-chain C and N-terminal. This arrangement of termini provide the insulin protein with a recognition site for the insulin receptor. Three mutations have been found to be key in the development of diabetes in humans. B-chain mutations of PheB24 changed to SerB24, PheB25 to LeuB25, and an A-chain mutation of ValA3 changed to LeuA3 are all correlated with impaired biological activity. Overall, this molecule has a non-polar interior and a polar exterior, mainly due to the make-up of the B-chain. Insulin’s quaternary structure is a hexamer formation of six insulin molecules in a life preserver shape. | These cysteine residues promote a parallel arrangement between A7-20 and B7-19, and more specifically the A6-A11 disulfide bond brings the C-terminal TyrA19 and the N-terminal GlyA1, IleA2, ValA3 closer together. Furthermore, the B-chain C-terminal of LeuB24, TyrB25, LeuB26 is brought near the A-chain C and N-terminal. This arrangement of termini provide the insulin protein with a recognition site for the insulin receptor. Three mutations have been found to be key in the development of diabetes in humans. B-chain mutations of PheB24 changed to SerB24, PheB25 to LeuB25, and an A-chain mutation of ValA3 changed to LeuA3 are all correlated with impaired biological activity. Overall, this molecule has a non-polar interior and a polar exterior, mainly due to the make-up of the B-chain. Insulin’s quaternary structure is a hexamer formation of six insulin molecules in a life preserver shape. | ||
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