Sandbox Reserved 766: Difference between revisions

<scene name='56/564042/Glutamine_amidotransferase/1'>Glutamine Amidotransferase Type-2</scene> (residues 2-191) and and <scene name='56/564042/Asparagine_synthetase_complex/1'>Asparagine Synthetase</scene> complex (residues 213-536). There are two specific domains that contain the substrate binding sites. The N-terminal domain which contains two layers of anti-parallel beta sheets comprised of six layers each, this is where the Glutamine binds. A C-terminal domain also exists, it is comprised of five parallel beta sheets with alpha helices on either side of it, <ref>"RCSB Protein Data Bank - RCSB PDB - 1CT9 Structure Summary." RCSB Protein Data Bank - RCSB PDB - 1CT9 Structure Summary. N.p., n.d. Web. 01 Dec. 2013.</ref> this is where the Mg2+, ATP and Aspartic Acid bind. The two active sites contained within the terminal domains are linked together by a tunnel of hydrophobic and polar surface amino acid residues. Specifically <scene name='56/564042/Residue_365/1'>Residue 365</scene> is important for the binding of the Beta-Asparty-AMP intermediate into the enzyme.  

The Entire amino acid sequence for this enzyme complex can be found below.<ref>"RCSB Protein Data Bank - RCSB PDB - 1CT9 Structure Summary." RCSB Protein Data Bank - RCSB PDB - 1CT9 Structure Summary. N.p., n.d. Web. 01 Dec. 2013.

'''Asparagine Synthetase''' catalyzes the interconversion of Aspartic Acid and Glutamine to Asparagine and Glutamic Acid. This is not a straight forward transferase reaction since the interconversion is not directly between Aspartic Acid and Glutamine. Instead this reaction more closely resembles a two part ATP dependent ligase reaction. ASNS has two distinct pockets; one where Adenosine Triphosphate (ATP) binds and is stabilized by the hydrogen bonds it forms with '''Ser 346''' (Gamma Oxygen) and amide groups of '''Val 272''', '''Leu 232''' and '''Gly 347'''. This binding of ATP to the N-Terminal domain is to stabilize the intermediate it forms with the Aspartic Acid; Beta-Aspartyl AMP (BAspAMP). This intermediate complex has to bind to the ASNS enzyme before the Glutamine binds into its pocket to establish coordination of the binding sites within the ASNS enzyme. After the BAspAMP intermediate binds in its pocket and establishes the coordination of the enzyme the Glutamine binds to its pocket in the C-Terminal domain and is stabilized specifically by its bonds with '''Arg 49''', '''Asn 74''', '''Glu 76''', and '''Asp 98''' residues. Once the substrates have been bound and stabilized free water hydrolyzes the amine group on the side chain of Glutamine causing the newly formed ammonia (NH3) group to detach leaving a carboxylate ion as the new functional group converting the Glutamine to Glutamate. The free Ammonia molecule then binds with the carbonyl carbon of the BAspAMP complex forcing the carbonyl carbon of the Aspartic Acid residue to favor the amine group both electrochemically and sterically and break its bond with the AMP releasing it, inorganic phosphate and forming a free Asparagine molecule, excess water in the environment then protonates the Glutamate into a free form Glutamic Acid molecule. This can be seen in the above right figure. The main difference between ASNS-B and ASNS-A is that instead of using Glutamine for the Nitrogen source for this reaction ASNS-A uses ammonia or diatomic Nitrogen directly.