Sandbox Reserved 962: Difference between revisions
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== Interaction == | == Interaction == | ||
=== Cap Analog Binding ( | === Cap Analog Binding (Guanosine 5'-Triphosphate)=== | ||
[[Image: | [[Image:]] | ||
<scene name='60/604481/Gtg/3'>A cap analog</scene> binds to the enzyme in a pocket near | <scene name='60/604481/Gtg/3'>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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{{clear}} | {{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}} | 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 N1, N3, and O6 atoms.{{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}} | ||
We remark also that the methyltransferase is not able to discrminate between ribose and deoxyribose nucleoside sugars. | We remark also that the methyltransferase is not able to discrminate between ribose and deoxyribose nucleoside sugars. | ||
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<scene name='60/604481/Interaction_sah/1'>10 amino acids</scene> (Lys54, Gly72, Asp78, Asp94, Ile95, Asp122, Ser124, Gln140, Phe141, Ser142) are involved in the stabilisation of AdoHcys. | <scene name='60/604481/Interaction_sah/1'>10 amino acids</scene> (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 : {{clear}} | The interactions between AdoHcys and the enzyme are made of : {{clear}} | ||
- Hydrogen bonds mediated by | - Hydrogen bonds mediated by <scene name='60/604481/Hd_sah/1'>Lys54, Gly72, Asp94, Asp122, Gln140</scene> {{clear}} | ||
<scene name='60/604481/Hd_sah/1'>Lys54, Gly72, Asp94, Asp122, Gln140</scene> {{clear}} | - Van der Walls interactions mediated by <scene name='60/604481/Vdw_sah/1'>Ile95, Tyr124 and Ser142</scene> {{clear}} | ||
- Van der Walls interactions mediated by | |||
<scene name='60/604481/Vdw_sah/1'>Ile95, Tyr124 and Ser142</scene> {{clear}} | |||
- An electrostatic interaction mediated by <scene name='60/604481/Elec_sah/1'>Gln140 and Phe141</scene> {{clear}} | - An electrostatic interaction mediated by <scene name='60/604481/Elec_sah/1'>Gln140 and Phe141</scene> {{clear}} | ||
- A water mediated contact mediated by <scene name='60/604481/Water_sah/1'>Asp78</scene> | - A water mediated contact mediated by <scene name='60/604481/Water_sah/1'>Asp78</scene> | ||
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== Mechanism== | == 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. {{clear}} | 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. {{clear}} | ||
We remark that there is no contact between the enzyme and the guanine N-7 nucleophile, | We remark that there is no contact between the enzyme and <scene name='60/604481/S_n7/1'>the guanine N-7 nucleophile, the AdoHcy sulfur leaving group</scene> or the AdoMet methyl carbon.{{clear}} | ||
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. | 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. | ||
