Sandbox Reserved 962

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=== AdoHcy Binding (S-Adenosyl-L-Homocysteine)===
=== AdoHcy Binding (S-Adenosyl-L-Homocysteine)===
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[[Image:Chemical_structure_AdoHcy.png]]
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[[Image:Chemical_structure_Adohcy.png]]
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The mRNA Cap Methyltransferase bind to <scene name='60/604481/Sah/2'>AdoHcy</scene> which is the product of the methyl donor AdoMet after the methylation.
The mRNA Cap Methyltransferase bind to <scene name='60/604481/Sah/2'>AdoHcy</scene> which is the product of the methyl donor AdoMet after the methylation.
AdoHcys is in a pocket formed by amino acids of segment 2.
AdoHcys is in a pocket formed by amino acids of segment 2.

Revision as of 09:52, 30 December 2014

This Sandbox is Reserved from 15/11/2014, through 15/05/2015 for use in the course "Biomolecule" taught by Bruno Kieffer at the Strasbourg University. This reservation includes Sandbox Reserved 951 through Sandbox Reserved 975.
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mRNA Cap (Guanine-N7) Methyltransferase (Ecm1)


Ecm1

Drag the structure with the mouse to rotate


Contents

Biological role

Structure

Interaction

Cap Analog Binding (7-Methylguanosine-5-Triphosphate-5-Guanosine)

Image:Chemical structure gpppg.png

binds to the enzyme in a pocket near the AdoHcy. (Tyr 145, Leu216, Leu217, Asp218, Ser219, Tyr284) are involded in the binding of the cap analog. The cap makes Van der Walls contacts, hydrogen bond and water mediated bond. [1]

As we can see on the figure, the enzyme specifically binds to guanine. This specificity is achieved through the recognition by the enzyme residues through hydrogen bonds of the guanine N1, N3, and O6 atoms. We remark also that the methyltransferase is not able to discrminate between ribose and deoxyribose nucleoside sugars.


AdoHcy Binding (S-Adenosyl-L-Homocysteine)

Image:Chemical structure Adohcy.png

The mRNA Cap Methyltransferase bind to which is the product of the methyl donor AdoMet after the methylation. AdoHcys is in a pocket formed by amino acids of segment 2. (Lys54, Gly72, Asp78, Asp94, Ile95, Asp122, Ser124, Gln140, Phe141, Ser142) are involved in the stabilisation of AdoHcys. The interactions between AdoHcys and the enzyme are made of : hydrogen bonds, Van der Walls interactions,electrostatic interaction and water mediated contact. [1]

Mechanism

This enzyme catalyse N-methyl transfer from AdoMet (S-adenosylmethionine) to GpppRNA, this reaction produce 7-methyl-GpppRNA and AdoHcy. This reaction is made trough a SN2 mechanism. We remark that there is no contact between the enzyme and the guanine N-7 nucleophile, the AdoMet methyl carbon, or the AdoHcy sulfur leaving group. Indeed the enzyme does not stabilize the transition state of the chemical reaction, does not promote the activation of the nucleophile or the explusion of the leaving group. mRNA Cap Methyltransferase brings the two substrates closer and orientates the substrates to facilitate the methyl transfer.

Inhibition

References

  1. 1.0 1.1 Fabrega C, Hausmann S, Shen V, Shuman S, Lima CD. Structure and mechanism of mRNA cap (guanine-N7) methyltransferase. Mol Cell. 2004 Jan 16;13(1):77-89. PMID:14731396
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