Sandbox Reserved 918: Difference between revisions

'''Dipeptidyl Peptidase IV''' (commonly abbreviated as '''DPP IV''') is a regulatory [http://en.wikipedia.org/wiki/Protease protease] and binding [http://en.wikipedia.org/wiki/Glycoprotein glycoprotein] that carries out numerous functions in humans making it a prime candidate for medicinal and pharmaceutical research. DPP IV, discovered by V.K. Hopsu-Havu and G.G. Glenner in homogenized rat liver tissue, was originally believed to serve a specific role in breaking [http://en.wikipedia.org/wiki/2-Naphthylamine 2-Naphthylamine] off of [http://brenda-enzymes.org/php/ligand_flatfile.php4?brenda_ligand_id=228740 Gly-Pro-2-napthylamide], hence its original name glycylproline napthylamidase. However, further research into the specificity of DPP IV eventually showed that it serves a more generic function as a [http://en.wikipedia.org/wiki/Hydrolase hydrolase] (a serine [http://en.wikipedia.org/wiki/Exopeptidase exopeptidase]), breaking  N-terminal Xaa-Pro bonds (though it can also catalyze alanine bonds). DPP IV is the founding member of the DPP-IV and/or structure homologue (DASH) family, who all share this serine protease catalysis of post-proline peptide bonds. <ref> PMID: 16186403</ref> These penultimate [http://en.wikipedia.org/wiki/Proline prolines] of the [http://en.wikipedia.org/wiki/N-terminus N-terminus] are known for their ability to resist attacks from most proteases and also induce a [http://en.wikipedia.org/wiki/Conformational_change conformational change] of their respective proteins. Therefore, DPP IV and its ability to catalyze said prolines gives it a unique specificity and target for pharmaceutical companies to take advantage of. <ref name="regpeps">PMID: 10588446</ref>

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/1'>Glu205-Glu206</scene>, form a small pocket where only small residues like proline or alanine will fit. <ref name="Gorrell">PMID: 15584901</ref> Examples of DPP IV substrates with alanine or proline at their N-terminus are: