Catechol 3-methyltransferase active site

Other Proteins The ouabain-binding site on (Na /K -adenosine-5 -triphosphatase, 46, 523 penicillin isocyanates for /3-lactamase, 46, 531 active site-directed addition of a small group to an enzyme the ethylation of ludferin, 46, 537 mandelate racemase, 46, 541 d imethylpyrazole carboxamidine and related derivatives, 46, 548 labeling of catechol O-methyltransferase with N-haloace-tyl derivatives, 46, 554 affinity labeling of binding sites in proteins by sensitized photooxidation, 46, 561 bromocolchicine as a iabei for tubuiin, 46, 567. 

The enzyme catechol-O-methyltransferase (COMT) is involved in pain regulation and regulation of neurotransmitters. COMT acts to catalyze the transfer of a methyl group from the cofactor S-adenosyl-L-methionine (SAM, 5) to the 0 of catecholate 4 (Reaction 9.5). The catechol structure is found in neurotransmitters such as dopamine, noradrenahne, and adrenaline. A related set of enzymes are the DNA methyltransferases that appear to have similar structure, especially in their active sites, to the structure of COMT. ... 

Rutherford K, Daggett V (2009) A hotspot of inactivation the A22S and V108M polymorphisms individually destabilize the active site structure of catechol O-methyltransferase. 

Figure 9. The active site of the enzyme catechol O-methyltransferase (PDB file 1VID), showing the binding of 3,4-dinitrocatechol and the relative dispositions of negatively charged Glul 99 and positively charged S-adenosylmethionine. (a) A simplified view, (b) A more extensive view of the active site, drawn in approximately the orientation of (a).

Lau, E.Y. and Bruice, T.C. (2000) Comparison of the dynamics for ground-state and transition-state structures of the active site of catechol-O-methyltransferase. J. Am. Chem. Soc. 122 7165-7171. 

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