Sandbox Reserved 918: Difference between revisions

The specificity of the DPP IV in its ability to discern the proline from other amino acids can be seen in the binding pocket where two glutamates, <scene name='57/573132/1x70_glutamates/3'>Glu205-Glu206</scene> orient the substrate allowing only small residues like proline or alanine to fit. The [http://en.wikipedia.org/wiki/Glutamic_acid glutamates] form a [http://en.wikipedia.org/wiki/Salt_bridge_(protein_and_supramolecular) salt bridge] with the N-terminus, positioning the substrate so that only two amino acids can fit into position for hydrolysis. <ref name="Gorrell">PMID: 15584901</ref> Examples of DPP IV substrates with alanine or proline at their N-terminus are:

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/1'>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"/>