Sandbox Reserved 497: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
Line 20: Line 20:


A proposed mechanism for the methyl transfer reaction catalyzed by DmdA has recently been published based on the known structural characteristics of DmdA as well as what is known about similar reactions, namely redox-neutral methyl transfer reactions involving THF as well reactions that involve a methyl transfer from a sulfonium atom to a nitrogen atom
A proposed mechanism for the methyl transfer reaction catalyzed by DmdA has recently been published based on the known structural characteristics of DmdA as well as what is known about similar reactions, namely redox-neutral methyl transfer reactions involving THF as well reactions that involve a methyl transfer from a sulfonium atom to a nitrogen atom
<ref> Schuller, D.J., Reisch, C.R., Moran, M.A., Whitman, W.B., Lanzilotta, W.N. (2012) Structures of dimethylsulfoniopropinate-dependent demethylase from the marine organism pelagabacter ubique. Protein Sci. 21: 289-298. </ref>. The proposed mechanism involves an SN2 intermediate with a concerted methyl group and a proton transfer mediated by a water molecule present in the active site.  
<ref> Schuller, D.J., Reisch, C.R., Moran, M.A., Whitman, W.B., Lanzilotta, W.N. (2012) Structures of dimethylsulfoniopropinate-dependent demethylase from the marine organism pelagabacter ubique. Protein Sci. 21: 289-298. </ref>. This proposed mechanism, as well as the reasoning behind it, is very similar to the mechanism for S-adenosylmethionine (SAM)-dependent N-methyltransferases. In particular, the proposed mechanism for the methyl transfer reaction catalyzed by DmdA involves an SN2 intermediate with a concerted methyl group and a proton transfer mediated by a water molecule present in the active site. This proposed reaction is logical due to the location of the active site, which is highly acessible by water, as well as the <scene name='Sandbox_Reserved_497/Acidicactivesite/1'>acidic side chains </scene> present in the active site. This presence of hydrogen bonds involving acidic residues polarizes the substrate thus lowering the enrgy barrier of the reaction and facilitating the mechanism for (SAM)-dependent N-methyltransferases and the homologous proposed mechanism for the DmdA enzymatic reaction. In addition, the proposed mechanism is also reasonable because the substrate for DmdA, DMSP, contains a sulfonium atom which tends to make methyl a fairly good leaving group.


[[Image:DmdA_Mechanism.jpg|thumb|500px|center|The proposed mechanism for the methyl transfer reaction catalyzed by DmdA. This image was obtained directly from Schuller et al.]]
[[Image:DmdA_Mechanism.jpg|thumb|500px|right|The proposed mechanism for the methyl transfer reaction catalyzed by DmdA. This image was obtained directly from Schuller et al.]]
 
This proposed reaction seems likely due to the location of the active site, which is highly acessible by water, as well as the <scene name='Sandbox_Reserved_497/Acidicactivesite/1'>acidic side chains </scene> present in the active site. Additionally the substrate for DmdA, DMSP, contains a sulfonium atom which tends to make methyl a fairly good leaving group.
 
 
 
S-adenosylmethionine (SAM)-dependent N-methyltransferases
The proposed mechanism for this reaction
 
 
Further support for this proposal comes
from the observation that a number of SAM-dependent
methyltransferases, such as protein arginine,
glycine-N, and phenylethanolamine-N methyltransferase
also help facilitate such a mechanism through
hydrogen bonds involving acidic residues,30,32,33 and
polarization of the nitrogen atom targeted for methyl
transfer. It has been proposed that polarization of
the substrate lowers the energy barrier to the SN2-
like methyl transfer reaction.34,35


==Possible Applications==
==Possible Applications==
Retrieved from "https://proteopedia.org/Sandbox_Reserved_497"