Sandbox 11: Difference between revisions
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The NAPase molecule provided shows two NAPase molecules that are mirror images, so here is just <scene name='Sandbox_11/Just_one/2'>one</scene>. NAPase, along with the rest of the trypsin family, has an active site that consists of the "catalytic triad." This <scene name='Sandbox_11/Catalytic_triad/2'>catalytic triad</scene> is made up of three amino acid residues (H57, D102, and S195) that play a major role in binding the substrate and catalyzing proteolysis. The distance between these residues on the protein chain, and the complexity of folding one might imagine is occurring, help to demonstrate the value of the Pro region. | The NAPase molecule provided shows two NAPase molecules that are mirror images, so here is just <scene name='Sandbox_11/Just_one/2'>one</scene>. NAPase, along with the rest of the trypsin family, has an active site that consists of the "catalytic triad." This <scene name='Sandbox_11/Catalytic_triad/2'>catalytic triad</scene> is made up of three amino acid residues (H57, D102, and S195) that play a major role in binding the substrate and catalyzing proteolysis. The distance between these residues on the protein chain, and the complexity of folding one might imagine is occurring, help to demonstrate the value of the Pro region. | ||
One of the major features of NAPase is that each protease has two domains, an N domain and a C domain. In this <scene name='Sandbox_11/Ntocrotatingone/1'>N to C Rainbow</scene>, one can see the N domain (red, orange, yellow), so-called because it contains the N-terminal amino acid, is connected covalently through the protein to the C domain (green, blue, violet). The horizontal axis of this scene is the main dividing line between the domains, with few chains crossing the barrier. It is important to note here that research suggests | One of the major features of NAPase is that each protease has two domains, an N domain and a C domain. In this <scene name='Sandbox_11/Ntocrotatingone/1'>N to C Rainbow</scene>, one can see the N domain (red, orange, yellow), so-called because it contains the N-terminal amino acid, is connected covalently through the protein to the C domain (green, blue, violet). The horizontal axis of this scene is the main dividing line between the domains, with few chains crossing the barrier. It is important to note here that research suggests the first step to unfolding is when the two domains split.<ref>PMID:20195497</ref> Just ask Professor Jaswal. | ||
Kelch (2007)<ref>PMID:17382344</ref>, looks at the differences between NAPase and αlp to try to understand what causes NAPase to be more acid resistant than αlp. It is found that they form a similar number of salt-bridges (7 in NAPase, 8 in αlp), but the salt bridges are in different places. Two of these bridges are conserved between the two, so there are five salt bridges that could be considered as important for acid resistance in NAPase. The important difference between the location of bridges is that αlp has three bridges that span the N and C domains, while NAPase has none that span the domains. <scene name='Sandbox_11/Two_salt_bridges/2'>This picture</scene> shows the charged residues of Glutamate and Arginine, with red representing a negative charge, and blue representing a positive charge. The distance between these residues is relatively small(avg. distance = 20 residues), when compared to the large distance between the residues in αlp (avg. distance = 78 residues). So, at low pH, the domain bridging salt bridges of αlp break or weaken enough that the N and C domains split apart enough for αlp to be protealyzed. NAPase avoids this with its alternately placed salt bridges, but surely this is not the only reason NAPase is more stabilized at low pH. And to make this page more fun, <scene name='Sandbox_11/Salt_bridge/1'>here</scene> is another salt bridge in NAPase. This one is the longest salt bridge in NAPase (57 residues), but it is between two residues that are both in the C domain. More importantly, if this bridge were to break, the nearby <scene name='Sandbox_11/Beta_sheet_at_c-terminus/1'>antiparallel β sheets</scene> and <scene name='Sandbox_11/Stabilizing_cysteine_bridge/1'>cysteine bridge</scene> would help to maintain the native state of NAPase. | Kelch (2007)<ref>PMID:17382344</ref>, looks at the differences between NAPase and αlp to try to understand what causes NAPase to be more acid resistant than αlp. It is found that they form a similar number of salt-bridges (7 in NAPase, 8 in αlp), but the salt bridges are in different places. Two of these bridges are conserved between the two, so there are five salt bridges that could be considered as important for acid resistance in NAPase. The important difference between the location of bridges is that αlp has three bridges that span the N and C domains, while NAPase has none that span the domains. <scene name='Sandbox_11/Two_salt_bridges/2'>This picture</scene> shows the charged residues of Glutamate and Arginine, with red representing a negative charge, and blue representing a positive charge. The distance between these residues is relatively small(avg. distance = 20 residues), when compared to the large distance between the residues in αlp (avg. distance = 78 residues). So, at low pH, the domain bridging salt bridges of αlp break or weaken enough that the N and C domains split apart enough for αlp to be protealyzed. NAPase avoids this with its alternately placed salt bridges, but surely this is not the only reason NAPase is more stabilized at low pH. And to make this page more fun, <scene name='Sandbox_11/Salt_bridge/1'>here</scene> is another salt bridge in NAPase. This one is the longest salt bridge in NAPase (57 residues), but it is between two residues that are both in the C domain. More importantly, if this bridge were to break, the nearby <scene name='Sandbox_11/Beta_sheet_at_c-terminus/1'>antiparallel β sheets</scene> and <scene name='Sandbox_11/Stabilizing_cysteine_bridge/1'>cysteine bridge</scene> would help to maintain the native state of NAPase. | ||