Glutaminase-Asparaginase (Pseudomonas 7A)
From Proteopedia
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| - | + | <StructureSection load='3pga' size='340' side='right' caption='Glutaminase-asparaginase (PDB code [[3pga]])' scene=''> | |
| - | <StructureSection load='3pga' size='340' side='right' caption=' | + | |
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== Function == | == Function == | ||
| - | L-asparaginase is an enzyme that converts L-asparagine into asparctic acid and ammonia. In adition this enzyme have a side activity analogous to previous one, which is the catalysis of D-glutamine into glutamate and ammonia. | + | '''L-asparaginase''' is an enzyme that converts L-asparagine into asparctic acid and ammonia. In adition this enzyme have a side activity analogous to previous one, which is the catalysis of D-glutamine into glutamate and ammonia. |
== Disease == | == Disease == | ||
Lymphoblastic Acute Leukemia, is a blood cancer that affects mainly childs (2-5 age); consists of non-controled proliferation of lymphocytic lineages since lymphoblasts to younges lymphocitic cells. | Lymphoblastic Acute Leukemia, is a blood cancer that affects mainly childs (2-5 age); consists of non-controled proliferation of lymphocytic lineages since lymphoblasts to younges lymphocitic cells. | ||
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Cancer cells are unable to perform synthesis of L-asparagine due to the lack of Asparagine Synthetase enzyme, which means that all source of L-asparagine is exogenous, unlike normal cells that can synthesize their own L-asparagine. When bacterial L-asparaginase is injected into the bloodstream, circulating L-asparagine is depleted, so cancer cells become unable to perform protein synthesis, that leads affected cells to apoptosis without harm to normal cells. | Cancer cells are unable to perform synthesis of L-asparagine due to the lack of Asparagine Synthetase enzyme, which means that all source of L-asparagine is exogenous, unlike normal cells that can synthesize their own L-asparagine. When bacterial L-asparaginase is injected into the bloodstream, circulating L-asparagine is depleted, so cancer cells become unable to perform protein synthesis, that leads affected cells to apoptosis without harm to normal cells. | ||
== Structural highlights == | == Structural highlights == | ||
| - | Pseudomonas 7A Glutaminase-Asparaginase (PGA) consists of a tetrameric structure. Each <scene name='79/790325/Monomer_3pga/1'>monomer</scene> is identical and possesses 337 residues. | + | ''Pseudomonas'' 7A '''Glutaminase-Asparaginase''' (PGA) consists of a tetrameric structure. Each <scene name='79/790325/Monomer_3pga/1'>monomer</scene> is identical and possesses 337 residues. |
In the amminoterminal portion of each monomer, is able to identify <scene name='79/790325/Beta_sheets_3pga/1'>10 beta-sheets</scene> and <scene name='79/790325/Alphahelix_3pga/1'>4 alpha-helix</scene>, unlike the carboxyl-terminal domain which have <scene name='79/790325/Beta_sheets_3pga/1'>4 beta sheets</scene> and <scene name='79/790325/Alphahelix_3pga/1'>4 alpha helix</scene>, you can also note that 5 beta-strands of the sheet are parallel and 4 are parallel. | In the amminoterminal portion of each monomer, is able to identify <scene name='79/790325/Beta_sheets_3pga/1'>10 beta-sheets</scene> and <scene name='79/790325/Alphahelix_3pga/1'>4 alpha-helix</scene>, unlike the carboxyl-terminal domain which have <scene name='79/790325/Beta_sheets_3pga/1'>4 beta sheets</scene> and <scene name='79/790325/Alphahelix_3pga/1'>4 alpha helix</scene>, you can also note that 5 beta-strands of the sheet are parallel and 4 are parallel. | ||
The PGA structure exhibit 4 active sites, they can be found in the intersection of monomers between the first and the third parallel beta sheets and loops from the carboxyl-terminal of the adjacent subunit, being the <scene name='79/790325/Flexible_loops_active_3pga/3'>residues 20-40</scene> the loop from carboxyl terminal and really important on catalysis due to their high flexibility; the main residues of this loop are Thr20, tyr34 and gly40. | The PGA structure exhibit 4 active sites, they can be found in the intersection of monomers between the first and the third parallel beta sheets and loops from the carboxyl-terminal of the adjacent subunit, being the <scene name='79/790325/Flexible_loops_active_3pga/3'>residues 20-40</scene> the loop from carboxyl terminal and really important on catalysis due to their high flexibility; the main residues of this loop are Thr20, tyr34 and gly40. | ||
In adition to flexible loop, there's a rigid group that takes part on catalysis and is represented by residues <scene name='79/790325/Active_site_residues_3pga/1'>Thr100, Asp101 and Lys173</scene>, which Thr100 plays as nucleophile, Lys173 is a base that enhance the nucleophilicity of Thr and Asp101 could stabilize the protonation state of Lys. | In adition to flexible loop, there's a rigid group that takes part on catalysis and is represented by residues <scene name='79/790325/Active_site_residues_3pga/1'>Thr100, Asp101 and Lys173</scene>, which Thr100 plays as nucleophile, Lys173 is a base that enhance the nucleophilicity of Thr and Asp101 could stabilize the protonation state of Lys. | ||
The flexible loop of active site plays a dual role, in the open conformation is responsible for substrate recognition, and in closed conformation is responsible for the proper spatial orientation of substrate in order to catalytic triad act the proper way. | The flexible loop of active site plays a dual role, in the open conformation is responsible for substrate recognition, and in closed conformation is responsible for the proper spatial orientation of substrate in order to catalytic triad act the proper way. | ||
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| - | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | ||
</StructureSection> | </StructureSection> | ||
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References
Lubkowski, J., Wlodawer, A., Ammon, H. L., Copeland, T. D., & Swain, A. L. (1994). Structural characterization of Pseudomonas 7A glutaminase-asparaginase. Biochemistry, 33(34), 10257-10265.
