Sandbox vdr: Difference between revisions

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==Mutation==

<StructureSection load='VDRmutation1.pdb' size='~~350~~' side='right' caption='Mutation of Vitamin D Receptor' scene=''>Amino acids like serine and threonine kinase plays a crucial role in signal transduction pathways drawn out by variety of growth factors, hormones, and neurotransmitters. When <scene name='56/562378/Vit_d_receptor_3m7r_serine/5'>serine</scene> is mutated it is replaced with a <scene name='56/562378/Vit_d_receptor_3m7r_serine/8'>glycine</scene> which results in an inhibition of transcriptional activation. When transcription is inhibited it results in p53 accumulation, which activates and promotes p53 translocation into mitochondria leading to apoptosis. Transcription inhibition is useful in cancer patients and so can be used as treatment option.

<StructureSection load='VDRmutation1.pdb' size='330' side='right' caption='Mutation of Vitamin D Receptor' scene=''>Amino acids like serine and threonine kinase plays a crucial role in signal transduction pathways drawn out by variety of growth factors, hormones, and neurotransmitters. When <scene name='56/562378/Vit_d_receptor_3m7r_serine/5'>serine</scene> is mutated it is replaced with a <scene name='56/562378/Vit_d_receptor_3m7r_serine/8'>glycine</scene> which results in an inhibition of transcriptional activation. When transcription is inhibited it results in p53 accumulation, which activates and promotes p53 translocation into mitochondria leading to apoptosis. Transcription inhibition is useful in cancer patients and so can be used as treatment option.

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==Crystal structure of the human VDR ligand binding domain bound to the synthetic agonist compound 2alpha-methyl-AMCR277A(C23S)==

<StructureSection load='3a3z' size='~~350~~' side='right' caption='Synthetic agonist (PDB entry [[3a3z]])' scene=''>Research showed that <scene name='56/562378/3a3z/1'>the synthetic analogue (20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (2a)</scene> acts as a 1alpha,25(OH)(2)D(3) superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1alpha,25(OH)(2)D(3), 2alpha-methyl-1alpha,25(OH)(2)D(3), or 2a, we designed a novel analogue, 2alpha-methyl-(20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes.

<StructureSection load='3a3z' size='330' side='right' caption='Synthetic agonist (PDB entry [[3a3z]])' scene=''>Research showed that <scene name='56/562378/3a3z/1'>the synthetic analogue (20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (2a)</scene> acts as a 1alpha,25(OH)(2)D(3) superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1alpha,25(OH)(2)D(3), 2alpha-methyl-1alpha,25(OH)(2)D(3), or 2a, we designed a novel analogue, 2alpha-methyl-(20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes.

</StructureSection>

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@@ Line 19: / Line 19: @@
 ==Mutation==
-<StructureSection load='VDRmutation1.pdb' size='350' side='right' caption='Mutation of Vitamin D Receptor' scene=''>Amino acids like serine and threonine kinase plays a crucial role in signal transduction pathways drawn out by variety of growth factors, hormones, and neurotransmitters. When <scene name='56/562378/Vit_d_receptor_3m7r_serine/5'>serine</scene> is mutated it is replaced with a <scene name='56/562378/Vit_d_receptor_3m7r_serine/8'>glycine</scene> which results in an inhibition of transcriptional activation. When transcription is inhibited it results in p53 accumulation, which activates and promotes p53 translocation into mitochondria leading to apoptosis. Transcription inhibition is useful in cancer patients and so can be used as treatment option.
+<StructureSection load='VDRmutation1.pdb' size='330' side='right' caption='Mutation of Vitamin D Receptor' scene=''>Amino acids like serine and threonine kinase plays a crucial role in signal transduction pathways drawn out by variety of growth factors, hormones, and neurotransmitters. When <scene name='56/562378/Vit_d_receptor_3m7r_serine/5'>serine</scene> is mutated it is replaced with a <scene name='56/562378/Vit_d_receptor_3m7r_serine/8'>glycine</scene> which results in an inhibition of transcriptional activation. When transcription is inhibited it results in p53 accumulation, which activates and promotes p53 translocation into mitochondria leading to apoptosis. Transcription inhibition is useful in cancer patients and so can be used as treatment option.
@@ Line 29: / Line 29: @@
 ==Crystal structure of the human VDR ligand binding domain bound to the synthetic agonist compound 2alpha-methyl-AMCR277A(C23S)==
-<StructureSection load='3a3z' size='350' side='right' caption='Synthetic agonist (PDB entry [[3a3z]])' scene=''>Research showed that <scene name='56/562378/3a3z/1'>the synthetic analogue (20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (2a)</scene> acts as a 1alpha,25(OH)(2)D(3) superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1alpha,25(OH)(2)D(3), 2alpha-methyl-1alpha,25(OH)(2)D(3), or 2a, we designed a novel analogue, 2alpha-methyl-(20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes.
+<StructureSection load='3a3z' size='330' side='right' caption='Synthetic agonist (PDB entry [[3a3z]])' scene=''>Research showed that <scene name='56/562378/3a3z/1'>the synthetic analogue (20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (2a)</scene> acts as a 1alpha,25(OH)(2)D(3) superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1alpha,25(OH)(2)D(3), 2alpha-methyl-1alpha,25(OH)(2)D(3), or 2a, we designed a novel analogue, 2alpha-methyl-(20S,23S)-epoxymethano-1alpha,25-dihydroxyvitamin D(3) (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes.
 </StructureSection>