Sandbox Reserved 962

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[[Image:GTP_structure.png]]
[[Image:GTP_structure.png]]
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<scene name='60/604481/Gtg/3'>A cap analog</scene> binds to the enzyme in a pocket near AdoHcy.{{clear}}
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<scene name='60/604481/Gtg/4'>A cap analog</scene> binds to the enzyme in a pocket near AdoHcy.{{clear}}
<scene name='60/604481/Interaction_gtg/2'>6 amino acids</scene> (Tyr 145, Leu216, Leu217, Asp218, Ser219, Tyr284) are involded in the binding of the cap analog. {{clear}}
<scene name='60/604481/Interaction_gtg/2'>6 amino acids</scene> (Tyr 145, Leu216, Leu217, Asp218, Ser219, Tyr284) are involded in the binding of the cap analog. {{clear}}
The cap makes Van der Walls contacts with side chains from <scene name='60/604481/Vdw_gtg/1'>Leu216, Leu217, Asp218, Ser219.</scene> {{clear}}
The cap makes Van der Walls contacts with side chains from <scene name='60/604481/Vdw_gtg/1'>Leu216, Leu217, Asp218, Ser219.</scene> {{clear}}
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<scene name='60/604481/Hb_gtg/1'>Tyr284</scene> makes a hydrogen bond and <scene name='60/604481/Water_gtg/1'>Tyr145</scene> a water mediated bond.
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GTP makes a hydrogen bond with <scene name='60/604481/Hb_gtg/1'>Tyr284</scene>and and a water mediated bond with<scene name='60/604481/Water_gtg/1'>Tyr145</scene>.
<ref name="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</ref>
<ref name="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</ref>
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As we can see on the figure above<ref name="Hausmann S, Zheng S, Fabrega C, Schneller SW, Lima CD, Shuman S. Encephalitozoon cuniculi mRNA cap (guanine N-7) methyltransferase: methyl acceptor specificity, inhibition BY S-adenosylmethionine analogs, and structure-guided mutational analysis. J Biol Chem. 2005 May 27;280(21):20404-12. Epub 2005 Mar 9.">PMID:15760890 </ref> , the enzyme specifically binds to guanine.{{clear}}
As we can see on the figure above<ref name="Hausmann S, Zheng S, Fabrega C, Schneller SW, Lima CD, Shuman S. Encephalitozoon cuniculi mRNA cap (guanine N-7) methyltransferase: methyl acceptor specificity, inhibition BY S-adenosylmethionine analogs, and structure-guided mutational analysis. J Biol Chem. 2005 May 27;280(21):20404-12. Epub 2005 Mar 9.">PMID:15760890 </ref> , the enzyme specifically binds to guanine.{{clear}}
This specificity is achieved through the recognition by the enzyme residues through hydrogen bonds of the guanine <scene name='60/604481/N1_n3_06_gtg/1'>N1, N3, and O6 atoms.</scene>{{clear}}
This specificity is achieved through the recognition by the enzyme residues through hydrogen bonds of the guanine <scene name='60/604481/N1_n3_06_gtg/1'>N1, N3, and O6 atoms.</scene>{{clear}}
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We remark also that the methyltransferase is not able to discrminate between ribose and deoxyribose nucleoside sugars.
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We remark also that the methyltransferase is not able to discrminate between ribose and desoxyribose nucleoside sugars.

Revision as of 12:47, 2 January 2015

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.
To get started:
  • Click the edit this page tab at the top. Save the page after each step, then edit it again.
  • Click the 3D button (when editing, above the wikitext box) to insert Jmol.
  • show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page.
  • Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc.

More help: Help:Editing


mRNA Cap (Guanine-N7) Methyltransferase (Ecm1)


Ecm1

Drag the structure with the mouse to rotate


Contents

Biological role

Structure

Interaction

Cap Analog Binding (Guanosine 5'-Triphosphate)

Image:GTP_structure.png

binds to the enzyme in a pocket near AdoHcy.
(Tyr 145, Leu216, Leu217, Asp218, Ser219, Tyr284) are involded in the binding of the cap analog.
The cap makes Van der Walls contacts with side chains from

GTP makes a hydrogen bond with and and a water mediated bond with. [1]

Image:Image methyl acceptor specificity.png

As we can see on the figure above[2] , the enzyme specifically binds to guanine.
This specificity is achieved through the recognition by the enzyme residues through hydrogen bonds of the guanine

We remark also that the methyltransferase is not able to discrminate between ribose and desoxyribose nucleoside sugars.


AdoHcy Binding (S-Adenosyl-L-Homocysteine)

Image:AdoHcy_nouveau.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 mediated by
- Van der Walls interactions mediated by
- An electrostatic interaction mediated by

- A water mediated contact mediated by [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 through a SN2 mechanism.
We remark that there is no contact between the enzyme and or the AdoMet methyl carbon.

Indeed the enzyme does not stabilize the transition state of the chemical reaction, does not promote the activation of the nucleophile or the expulsion of the leaving group. mRNA Cap Methyltransferase brings the two substrates closer and orientates the substrates to facilitate the methyl transfer.



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
  2. ↑ Hausmann S, Zheng S, Fabrega C, Schneller SW, Lima CD, Shuman S. Encephalitozoon cuniculi mRNA cap (guanine N-7) methyltransferase: methyl acceptor specificity, inhibition BY S-adenosylmethionine analogs, and structure-guided mutational analysis. J Biol Chem. 2005 May 27;280(21):20404-12. Epub 2005 Mar 9. PMID:15760890 doi:10.1074/jbc.M501073200
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