DOPA decarboxylase: Difference between revisions

The mechanism of DDC catalyzed decarboxylation of L-Dopa to Dopamine has been well-studied due to the enzymes role in PD. Shown below is the mechanism of decarboxylation, as determined by several experimental approaches, including site-directed mutagenesis, UV-Vis Spectroscopy, X-Ray Crystallography, Multiple Sequence Alignment, and Stopped-Flow Spectroscopy. [[image:slide1.png|thumb|center|500px|]] Once again, the transimination step (conversion of internal to external aldimine) is common to all PLP-dependent enzymes. The subsequent orientation of the quinonoid intermediate allows for stereospecific decarboxylation of the substrate at the alpha carbon, as predicted by '''Dunathan's stereoelectronic hypothesis''' <ref name="dunathan">PMID:224217 </ref>, in which he proposed that the substrate binds PLP such that the bond made around the Cα that is going to be broken is aligned with the pi orbital system of the cofactor.  

[[image:Dunathan.png|thumb|left|300px|'''Dunathan's Stereoeletronic Hypothesis, 1966''']] This way, the developing p orbital is aligned for maximal overlap with the extended p system, lowering the energy of the transition state and increasing the rate of the reaction. As well, by controlling substrate orientation, the enzyme can distinguish between '''deprotonation''' and '''decarboxylation'''.

===Critical Residues===