Sandbox Reserved 962: Difference between revisions
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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/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, more precisely they interact with guanine<scene name='60/604481/N1_n3_06_gtg/1'>N1, N3, and O6 atoms.</scene>{{clear}} and with the guanine exocyclic 2-NH2. {{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, more precisely they interact with guanine <scene name='60/604481/N1_n3_06_gtg/1'>N1, N3, and O6 atoms.</scene>{{clear}} and with the guanine exocyclic 2-NH2. {{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}} | ||
GTP makes a hydrogen bond with <scene name='60/604481/Hb_gtg/1'>Tyr284</scene> and a water mediated bond with <scene name='60/604481/Water_gtg/1'>Tyr145</scene>. | GTP makes a hydrogen bond with <scene name='60/604481/Hb_gtg/1'>Tyr284</scene> and a water mediated bond with <scene name='60/604481/Water_gtg/1'>Tyr145</scene>. | ||
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*'''AdoHcy'''{{clear}} | *'''AdoHcy'''{{clear}} | ||
It was show that the methylation of GTP increase with the concentration of AdoMet (Km of 25μM) and it was determined that the product AdoHcy has a similar affinity than AdoMet. But the activity of Ecm1 is inhibited by AdoHcy in a concentration-dependant way and the apparent IC50 was 4μm. | It was show that the methylation of GTP increase with the concentration of AdoMet (Km of 25μM) and it was determined that the product AdoHcy has a similar affinity than AdoMet. But the activity of Ecm1 is inhibited by AdoHcy in a concentration-dependant way and the apparent IC50 was 4μm.<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> {{clear}} | ||
<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> {{clear}} | |||
* '''Sinefugin'''{{clear}} | * '''Sinefugin'''{{clear}} | ||
Sinefugin, an analog of AdoMet differs from AdoMet only in the S-CH3 which is replaced by a C-NH2. It was show that sinefugin inhibit Ecm1 in a concentration-dependant manner too, the apparent IC50 is 1.5μm. The Ecm1 has an affinity for sinefugin 2/3 fold higher than for AdoMet and AdoHcy. Sinefugin has been shown to have antifungal, antiprotozoal and antiviral activities, these activities is probably related to his capacity to inhibit a variety of AdoMet-dependent methyltransferase. | Sinefugin, an analog of AdoMet differs from AdoMet only in the S-CH3 which is replaced by a C-NH2. It was show that sinefugin inhibit Ecm1 in a concentration-dependant manner too, the apparent IC50 is 1.5μm. The Ecm1 has an affinity for sinefugin 2/3 fold higher than for AdoMet and AdoHcy. Sinefugin has been shown to have antifungal, antiprotozoal and antiviral activities, these activities is probably related to his capacity to inhibit a variety of AdoMet-dependent methyltransferase.<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>{{clear}} | ||
<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>{{clear}} | |||
*'''Aza-AdoMet & carbocyclic aza-AdoMet'''{{clear}} | *'''Aza-AdoMet & carbocyclic aza-AdoMet'''{{clear}} | ||
Aza-AdoMet and carbocyclic aza-AdoMet are analogs of AdoMet too. In these two molecules the sulfur atom is replaced by nitrogen. And in the carbocyclic derivate the O4-atom of the ribose is replaced by a methylene group. These two molecules are weak inhibitorsof Ecm1. The IC50 values of Aza-AdoMet is 100μm and of carbocyclic aza-AdoMet is 35μm | Aza-AdoMet and carbocyclic aza-AdoMet are analogs of AdoMet too. In these two molecules the sulfur atom is replaced by nitrogen. And in the carbocyclic derivate the O4-atom of the ribose is replaced by a methylene group. These two molecules are weak inhibitorsof Ecm1. The IC50 values of Aza-AdoMet is 100μm and of carbocyclic aza-AdoMet is 35μm | ||
<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> | <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> | ||
</StructureSection> | |||
== References == | == References == | ||
<references/> | <references/> | ||
== Proteopedia page contributors and editors == | |||
Aline Girardet & Laure Hertzog | |||
