User:Alexander Rudecki/Sandbox 1: Difference between revisions

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The <scene name='58/580851/Composition/1'>composition</scene> of DromeQC consists of either {{Template:ColorKey Composition Protein}}, {{Template:ColorKey Composition Ligand}}, or {{Template:ColorKey Composition Solvent}} in which it was crystallized (water). When DromeQC <scene name='58/580851/Secondary/1'>secondary structure</scene> is colour coated ({{Template:ColorKey_Helix}}, {{Template:ColorKey_Strand}}) the global fold may be visualized nicely. This fold is driven by <scene name='58/580851/Polar/1'>hydrophobic/polar</scene> residues. The majority of {{Template:ColorKey_Hydrophobic}} residues lie in the interior, consistent with the hydrophobic collapse folding theory. Likewise, most {{Template:ColorKey_Polar}} residues reside on the exterior where they contact polar solvent molecules. Similarly, <scene name='58/580851/Charge/1'>charged residues</scene>, either {{Template:ColorKey_Charge_Anionic}} or {{Template:ColorKey_Charge_Cationic}} appear to cluster on the outside of the protein. From ~~these analyses~~, it can be seen that a salt bridge connects the two monomers.

The <scene name='58/580851/Composition/1'>composition</scene> of DromeQC consists of either {{Template:ColorKey Composition Protein}}, {{Template:ColorKey Composition Ligand}}, or {{Template:ColorKey Composition Solvent}} in which it was crystallized (water). When DromeQC <scene name='58/580851/Secondary/1'>secondary structure</scene> is colour coated ({{Template:ColorKey_Helix}}, {{Template:ColorKey_Strand}}) the global fold may be visualized nicely. This fold is driven by <scene name='58/580851/Polar/1'>hydrophobic/polar</scene> residues. The majority of {{Template:ColorKey_Hydrophobic}} residues lie in the interior, consistent with the hydrophobic collapse folding theory. Likewise, most {{Template:ColorKey_Polar}} residues reside on the exterior where they contact polar solvent molecules. Similarly, <scene name='58/580851/Charge/1'>charged residues</scene>, either {{Template:ColorKey_Charge_Anionic}} or {{Template:ColorKey_Charge_Cationic}} appear to cluster on the outside of the protein. From analysis of charged residues, it can be seen that a salt bridge connects the two monomers.

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[[Image:Cropped_dimer.jpg|thumb|400px|right|Figure 2. A 3D graphical representation displaying the homodimer glutaminyl cyclase from ''Drosophila melanogaster'' (PDB: 4F9U). Secondary structure is depicted by red (α-helix) and yellow (β-strand) ribbons, glycosyl groups are coloured pinks, while hydrogen bonds between the two monomers are shown by dotted green lines. The active site of QC contains a chelated zinc ion represented by a gray sphere. Also bound to the active site of this crystal structure and depicted as blue is the inhibitor 1-(3,4-dimethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea.]][[Image:DromeQCActiveSite.png|thumb|300px|left|Figure 3. A comparison between the active sites of Drosophila melanogaster DromeQC crystalized either with a PBD150 inhibitor (right, 4F90) or without (left, 4FWU). Protein loops surrounding the active site are denoted in blue, and a key catalytic Zn2+ is shown as a grey sphere, chelated by three residues shown in light blue. The PBD150 inhibitor (red) involve interactions with W296 (yellow), F292 (green), W176 (beige) and D271 (pink).]]

[[Image:Cropped_dimer.jpg|thumb|400px|right|Figure 2. A 3D graphical representation displaying the homodimer glutaminyl cyclase from ''Drosophila melanogaster'' (PDB: 4F9U). Secondary structure is depicted by red (α-helix) and yellow (β-strand) ribbons, glycosyl groups are coloured pinks, while hydrogen bonds between the two monomers are shown by dotted green lines. The active site of QC contains a chelated zinc ion represented by a gray sphere. Also bound to the active site of this crystal structure and depicted as blue is the inhibitor 1-(3,4-dimethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea.]][[Image:DromeQCActiveSite.png|thumb|300px|left|Figure 4. A comparison between the active sites of Drosophila melanogaster DromeQC crystalized either with a PBD150 inhibitor (right, 4F90) or without (left, 4FWU). Protein loops surrounding the active site are denoted in blue, and a key catalytic Zn2+ is shown as a grey sphere, chelated by three residues shown in light blue. The PBD150 inhibitor (red) involve interactions with W296 (yellow), F292 (green), W176 (beige) and D271 (pink).]]

===Topology and Overall Structure===

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The active site of DromeQC is located on four loops that lack secondary structure (Figure 4). Using these loops as a scaffold, a catalytic zinc ion is chelated via D131 OD2, E171 OE2, and H297 NE2. Thus, under the absence of substrate or inhibitor, Zn2+ exhibits trivalency (Figure 4). However, when DromeQC was crystalized in presence of a PBD150 inhibitor, Zn2+ was additionally chelated by the PBD150 imidazole moiety<ref name="main"/>. It is plausible that the amide oxygen of glutamine of peptide substrates chelate the zinc ion in a similar fashion, leading to position, polarization, and stabilization for cyclization.

[[Image:QCActiveSite.png|thumb|700px|center|Figure 4. A comparison between the active sites of Drosophila melanogaster DromeQC crystalized either with a PBD150 inhibitor (right, 4F90) or without (left, 4FWU). Protein loops surrounding the active site are denoted in blue, and a key catalytic Zn2+ is shown as a grey sphere, chelated by three residues shown in light blue. The PBD150 inhibitor (red) involve interactions with W296 (yellow), F292 (green), W176 (beige) and D271 (pink).]]

==Function==

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-The <scene name='58/580851/Composition/1'>composition</scene> of DromeQC consists of either <span style="font-size:150%">{{Template:ColorKey Composition Protein}}, {{Template:ColorKey Composition Ligand}}</span>, or <span style="font-size:150%">{{Template:ColorKey Composition Solvent}}</span> in which it was crystallized (water). When DromeQC <scene name='58/580851/Secondary/1'>secondary structure</scene> is colour coated <span style="font-size:150%">({{Template:ColorKey_Helix}}, {{Template:ColorKey_Strand}})</span> the global fold may be visualized nicely. This fold is driven by <scene name='58/580851/Polar/1'>hydrophobic/polar</scene> residues. The majority of <span style="font-size:150%">{{Template:ColorKey_Hydrophobic}}</span> residues lie in the interior, consistent with the hydrophobic collapse folding theory. Likewise, most <span style="font-size:150%">{{Template:ColorKey_Polar}}</span> residues reside on the exterior where they contact polar solvent molecules. Similarly, <scene name='58/580851/Charge/1'>charged residues</scene>, either <span style="font-size:150%">{{Template:ColorKey_Charge_Anionic}}</span> or <span style="font-size:150%">{{Template:ColorKey_Charge_Cationic}}</span> appear to cluster on the outside of the protein. From these analyses, it can be seen that a salt bridge connects the two monomers.
+The <scene name='58/580851/Composition/1'>composition</scene> of DromeQC consists of either <span style="font-size:150%">{{Template:ColorKey Composition Protein}}, {{Template:ColorKey Composition Ligand}}</span>, or <span style="font-size:150%">{{Template:ColorKey Composition Solvent}}</span> in which it was crystallized (water). When DromeQC <scene name='58/580851/Secondary/1'>secondary structure</scene> is colour coated <span style="font-size:150%">({{Template:ColorKey_Helix}}, {{Template:ColorKey_Strand}})</span> the global fold may be visualized nicely. This fold is driven by <scene name='58/580851/Polar/1'>hydrophobic/polar</scene> residues. The majority of <span style="font-size:150%">{{Template:ColorKey_Hydrophobic}}</span> residues lie in the interior, consistent with the hydrophobic collapse folding theory. Likewise, most <span style="font-size:150%">{{Template:ColorKey_Polar}}</span> residues reside on the exterior where they contact polar solvent molecules. Similarly, <scene name='58/580851/Charge/1'>charged residues</scene>, either <span style="font-size:150%">{{Template:ColorKey_Charge_Anionic}}</span> or <span style="font-size:150%">{{Template:ColorKey_Charge_Cationic}}</span> appear to cluster on the outside of the protein. From analysis of charged residues, it can be seen that a salt bridge connects the two monomers.
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-[[Image:Cropped_dimer.jpg|thumb|400px|right|Figure 2. A 3D graphical representation displaying the homodimer glutaminyl cyclase from ''Drosophila melanogaster'' (PDB: 4F9U). Secondary structure is depicted by red (α-helix) and yellow (β-strand) ribbons, glycosyl groups are coloured pinks, while hydrogen bonds between the two monomers are shown by dotted green lines. The active site of QC contains a chelated zinc ion represented by a gray sphere. Also bound to the active site of this crystal structure and depicted as blue is the inhibitor 1-(3,4-dimethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea.]][[Image:DromeQCActiveSite.png|thumb|300px|left|Figure 3. A comparison between the active sites of Drosophila melanogaster DromeQC crystalized either with a PBD150 inhibitor (right, 4F90) or without (left, 4FWU). Protein loops surrounding the active site are denoted in blue, and a key catalytic Zn<sup>2+</sup> is shown as a grey sphere, chelated by three residues shown in light blue. The PBD150 inhibitor (red) involve interactions with W296 (yellow), F292 (green), W176 (beige) and D271 (pink).]]
+[[Image:Cropped_dimer.jpg|thumb|400px|right|Figure 2. A 3D graphical representation displaying the homodimer glutaminyl cyclase from ''Drosophila melanogaster'' (PDB: 4F9U). Secondary structure is depicted by red (α-helix) and yellow (β-strand) ribbons, glycosyl groups are coloured pinks, while hydrogen bonds between the two monomers are shown by dotted green lines. The active site of QC contains a chelated zinc ion represented by a gray sphere. Also bound to the active site of this crystal structure and depicted as blue is the inhibitor 1-(3,4-dimethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea.]][[Image:DromeQCActiveSite.png|thumb|300px|left|Figure 4. A comparison between the active sites of Drosophila melanogaster DromeQC crystalized either with a PBD150 inhibitor (right, 4F90) or without (left, 4FWU). Protein loops surrounding the active site are denoted in blue, and a key catalytic Zn<sup>2+</sup> is shown as a grey sphere, chelated by three residues shown in light blue. The PBD150 inhibitor (red) involve interactions with W296 (yellow), F292 (green), W176 (beige) and D271 (pink).]]
 ===Topology and Overall Structure===
@@ Line 41: / Line 41: @@
 The active site of DromeQC is located on four loops that lack secondary structure (Figure 4). Using these loops as a scaffold, a catalytic zinc ion is chelated via D131 OD2, E171 OE2, and H297 NE2. Thus, under the absence of substrate or inhibitor, Zn<sup>2+</sup> exhibits trivalency (Figure 4). However, when DromeQC was crystalized in presence of a PBD150 inhibitor, Zn<sup>2+</sup> was additionally chelated by the PBD150 imidazole moiety<ref name="main"/>. It is plausible that the amide oxygen of glutamine of peptide substrates chelate the zinc ion in a similar fashion, leading to position, polarization, and stabilization for cyclization.
-[[Image:QCActiveSite.png|thumb|700px|center|Figure 4. A comparison between the active sites of Drosophila melanogaster DromeQC crystalized either with a PBD150 inhibitor (right, 4F90) or without (left, 4FWU). Protein loops surrounding the active site are denoted in blue, and a key catalytic Zn<sup>2+</sup> is shown as a grey sphere, chelated by three residues shown in light blue. The PBD150 inhibitor (red) involve interactions with W296 (yellow), F292 (green), W176 (beige) and D271 (pink).]]
 ==Function==