Sandbox 11: Difference between revisions

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Eran Hodis, Student

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 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.  The distance between the residues of each individual salt bridge in NAPase is relatively small(avg. distance = 20 residues), when compared to the large distance between the residues in αLP (avg. distance = 78 residues).  <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.
+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.  The distance between the residues of each individual salt bridge in NAPase is relatively small(avg. distance = 20 residues), when compared to the large distance between the residues in αLP (avg. distance = 78 residues).  <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.
 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 alternate placement of salt bridges.  Of course, there may be more reasons for the added acid resistance, but those are as yet undetermined. 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.