Sandbox Reserved 918: Difference between revisions
No edit summary |
No edit summary |
||
| Line 58: | Line 58: | ||
In addition to the glutamates holding the substrate in close proximity, and the catalytic triad using acid base chemistry to cleave the peptide bond, there is a tyrosine, <scene name='57/573132/1x70_activesitetyr/3'>Tyr547</scene>, which is depicted in orange and notably only 4.08 [http://en.wikipedia.org/wiki/Angstrom angstroms] away from the substrate, [http://en.wikipedia.org/wiki/Sitagliptin Sitagliptin]. Based off of the crystal structure, this tyrosine is believed to stabilize the tetrahedral intermediate, another important function in enzymatic processes. <ref name="Gorrell"/> The active site in its entirety is considered to contain residues 39-51 and 501-766 and is known as the <scene name='57/573132/1x70_alphabetaprop/1'>α/β-hydrolase domain</scene> | In addition to the glutamates holding the substrate in close proximity, and the catalytic triad using acid base chemistry to cleave the peptide bond, there is a tyrosine, <scene name='57/573132/1x70_activesitetyr/3'>Tyr547</scene>, which is depicted in orange and notably only 4.08 [http://en.wikipedia.org/wiki/Angstrom angstroms] away from the substrate, [http://en.wikipedia.org/wiki/Sitagliptin Sitagliptin]. Based off of the crystal structure, this tyrosine is believed to stabilize the tetrahedral intermediate, another important function in enzymatic processes. <ref name="Gorrell"/> The active site in its entirety is considered to contain residues 39-51 and 501-766 and is known as the <scene name='57/573132/1x70_alphabetaprop/1'>α/β-hydrolase domain</scene> | ||
Lastly, the <scene name='57/573132/1x70_basic_dimer/1'>homodimerization</scene> (colored by monomer) of DPP IV is critical to the catalytic function. Though whole domains play key roles in the formation of this dimer, single residues like (<scene name='57/573132/1x70_his750/1'>His750</scene>) have also been shown to be key to formation of the dimer. If [http://en.wikipedia.org/wiki/Point_mutation point mutated] to glutamate, the dimer will not form. The [http://en.wikipedia.org/wiki/Ionic_bonding ionic] | Lastly, the <scene name='57/573132/1x70_basic_dimer/1'>homodimerization</scene> (colored by monomer) of DPP IV is critical to the catalytic function. Though whole domains play key roles in the formation of this dimer, single residues like (<scene name='57/573132/1x70_his750/1'>His750</scene>) have also been shown to be key to formation of the dimer. If [http://en.wikipedia.org/wiki/Point_mutation point mutated] to glutamate, the dimer will not form. The [http://en.wikipedia.org/wiki/Ionic_bonding ionic] interactions of the histidine with the opposing chain are changed from electrostatically positive to a repulsive effect thus eliminating the ability to dimerize. <ref name="Gorrell"/> | ||
===Propeller Domain=== | ===Propeller Domain=== | ||
Though DPP IV's primary function is as a hydrolase, it also serves as a [http://en.wikipedia.org/wiki/Transmembrane_protein transmembrane] glycoprotein on the surface of cells. A specific domain, the <scene name='57/573132/1x70_8bladed/2'>8-bladed β-propeller domain</scene>, works in binding the most well known DPP IV ligand, [http://en.wikipedia.org/wiki/Adenosine_deaminase adenosine deaminase] (or ADA). ADA can bind to either the monomer or dimer of DPP IV because each monomer contains the 8-bladed propeller domain. ADA actually binds to the lower side of this domain, at the fourth and fifth propeller. Adenosine deaminase works to deaminate adenosine into [http://en.wikipedia.org/wiki/Inosine inosine], an important function in [http://en.wikipedia.org/wiki/Purine_metabolism purine metabolism], however it's most important role in humans deals with the immune system. ADA is a well understood enzyme that is highly conserved across numerous species in the body, yet it's binding to DPP IV is not completely understood and there is no known reason as to why it occurs. One theory is that binding ADA to the DPP IV glycoprotein inhibits its catalytic function, increasing the concentration of extracellular adenosine which plays a role in [http://en.wikipedia.org/wiki/T_cell T-cell] proliferation. <ref name="Gorrell"/> | Though DPP IV's primary function is as a hydrolase, it also serves as a [http://en.wikipedia.org/wiki/Transmembrane_protein transmembrane] glycoprotein on the surface of cells. A specific domain, the <scene name='57/573132/1x70_8bladed/2'>8-bladed β-propeller domain</scene>, works in binding the most well known DPP IV ligand, [http://en.wikipedia.org/wiki/Adenosine_deaminase adenosine deaminase] (or ADA). <ref name="Gorrell"/> ADA can bind to either the monomer or dimer of DPP IV because each monomer contains the 8-bladed propeller domain. ADA actually binds to the lower side of this domain, at the fourth and fifth propeller. Adenosine deaminase works to deaminate adenosine into [http://en.wikipedia.org/wiki/Inosine inosine], an important function in [http://en.wikipedia.org/wiki/Purine_metabolism purine metabolism], however it's most important role in humans deals with the immune system. ADA is a well understood enzyme that is highly conserved across numerous species in the body, yet it's binding to DPP IV is not completely understood and there is no known reason as to why it occurs. One theory is that binding ADA to the DPP IV glycoprotein inhibits its catalytic function, increasing the concentration of extracellular adenosine which plays a role in [http://en.wikipedia.org/wiki/T_cell T-cell] proliferation. <ref name="Gorrell"/> | ||
</StructureSection> | </StructureSection> | ||