User:Alexander Rudecki/Sandbox 1: Difference between revisions

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===Topology and Overall Structure<ref name="main"/>===

As shown above, DromeQC is made up of 2 identical, independent monomers that come together to form an asymmetric <scene name='58/580851/Two_chains/2'>homodimer</scene> (Figure 1). The subunits are connected via 4 hydrogen bonds (Chain A→Chain B: ARG35 NH2→GLU64 OE2, ARG43 NH2→ASN71 O, ARG43 NH2→PHE75 O, ARG43 NH1→PHE75 O) and surface complementarity (Figure 2). The subunits exhibit a globular α/β-hydrolase fold, characterized by a central twisted β-sheet motif consisting of 5 parallel strands (β1 and β3-β6) and an antiparallel β2 strand (Figures 2&3). This β-center is flanked by 9 surrounding α-helices; 2 fill the concave face (α5, α7), 7 fill the convex face (α1- α5, α8, α9) with one helix at the edge (α6) of each monomer. DromeQC is glycosylated (with up to 7 carbohydrate moieties) at the N42 position. These polysaccharide tags increase the solubility of DromeQC, and appear to have no affect of protein activity~~<ref name="main"/>~~.

As shown above, DromeQC is made up of 2 identical, independent monomers that come together to form an asymmetric <scene name='58/580851/Two_chains/2'>homodimer</scene> (Figure 1). The subunits are connected via 4 hydrogen bonds (Chain A→Chain B: ARG35 NH2→GLU64 OE2, ARG43 NH2→ASN71 O, ARG43 NH2→PHE75 O, ARG43 NH1→PHE75 O) and surface complementarity (Figure 2). The subunits exhibit a globular α/β-hydrolase fold, characterized by a central twisted β-sheet motif consisting of 5 parallel strands (β1 and β3-β6) and an antiparallel β2 strand (Figures 2&3). This β-center is flanked by 9 surrounding α-helices; 2 fill the concave face (α5, α7), 7 fill the convex face (α1- α5, α8, α9) with one helix at the edge (α6) of each monomer. DromeQC is glycosylated (with up to 7 carbohydrate moieties) at the N42 position. These polysaccharide tags increase the solubility of DromeQC, and appear to have no affect of protein activity.

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===Inhibitor binding<ref name="main"/>===

Binding of PBD150 to DromeQC utilizes π-π, arene-H, and hydrogen bonding interactions (Figure 4). The dimethoxyphenyl phenyl group of PBD150 is stabilized by π-π interactions with F292. This phenyl group is highly flexibily, however, as only weak electron density was observed during crystal structure analysis~~<ref name="main"/>~~. Such flexibility could be essential for substrates to cyclize. Also stabilizing the inhibitor is an arene-H interaction made between the imidazole moiety of PBD150 and W296. The first carbon upstream of this imidazole ring forms an additional arene-H contact with W176. Finally, the sulfur contained in the thiourea group makes a hydrogen bond with D271. This sulfur could mimic a carbonyl oxygen in the backbone of a peptide, suggesting a possible substrate binding mechanism.

Binding of PBD150 to DromeQC utilizes π-π, arene-H, and hydrogen bonding interactions (Figure 4). The dimethoxyphenyl phenyl group of PBD150 is stabilized by π-π interactions with F292. This phenyl group is highly flexibily, however, as only weak electron density was observed during crystal structure analysis. Such flexibility could be essential for substrates to cyclize. Also stabilizing the inhibitor is an arene-H interaction made between the imidazole moiety of PBD150 and W296. The first carbon upstream of this imidazole ring forms an additional arene-H contact with W176. Finally, the sulfur contained in the thiourea group makes a hydrogen bond with D271. This sulfur could mimic a carbonyl oxygen in the backbone of a peptide, suggesting a possible substrate binding mechanism.

==Function==

@@ Line 33: / Line 33: @@
 ===Topology and Overall Structure<ref name="main"/>===
-As shown above, DromeQC is made up of 2 identical, independent monomers that come together to form an asymmetric <scene name='58/580851/Two_chains/2'>homodimer</scene> (Figure 1). The subunits are connected via 4 hydrogen bonds (Chain A→Chain B: ARG35 NH2→GLU64 OE2, ARG43 NH2→ASN71 O, ARG43 NH2→PHE75 O, ARG43 NH1→PHE75 O) and surface complementarity (Figure 2). The subunits exhibit a globular α/β-hydrolase fold, characterized by a central twisted β-sheet motif consisting of 5 parallel strands (β1 and β3-β6) and an antiparallel β2 strand (Figures 2&3). This β-center is flanked by 9 surrounding α-helices; 2 fill the concave face (α5, α7), 7 fill the convex face (α1- α5, α8, α9) with one helix at the edge (α6) of each monomer. DromeQC is glycosylated (with up to 7 carbohydrate moieties) at the N42 position. These polysaccharide tags increase the solubility of DromeQC, and appear to have no affect of protein activity<ref name="main"/>.
+As shown above, DromeQC is made up of 2 identical, independent monomers that come together to form an asymmetric <scene name='58/580851/Two_chains/2'>homodimer</scene> (Figure 1). The subunits are connected via 4 hydrogen bonds (Chain A→Chain B: ARG35 NH2→GLU64 OE2, ARG43 NH2→ASN71 O, ARG43 NH2→PHE75 O, ARG43 NH1→PHE75 O) and surface complementarity (Figure 2). The subunits exhibit a globular α/β-hydrolase fold, characterized by a central twisted β-sheet motif consisting of 5 parallel strands (β1 and β3-β6) and an antiparallel β2 strand (Figures 2&3). This β-center is flanked by 9 surrounding α-helices; 2 fill the concave face (α5, α7), 7 fill the convex face (α1- α5, α8, α9) with one helix at the edge (α6) of each monomer. DromeQC is glycosylated (with up to 7 carbohydrate moieties) at the N42 position. These polysaccharide tags increase the solubility of DromeQC, and appear to have no affect of protein activity.
@@ Line 44: / Line 44: @@
 ===Inhibitor binding<ref name="main"/>===
-Binding of PBD150 to DromeQC utilizes π-π, arene-H, and hydrogen bonding interactions (Figure 4). The dimethoxyphenyl phenyl group of PBD150 is stabilized by π-π interactions with F292. This phenyl group is highly flexibily, however, as only weak electron density was observed during crystal structure analysis<ref name="main"/>. Such flexibility could be essential for substrates to cyclize. Also stabilizing the inhibitor is an arene-H interaction made between the imidazole moiety of PBD150 and W296. The first carbon upstream of this imidazole ring forms an additional arene-H contact with W176. Finally, the sulfur contained in the thiourea group makes a hydrogen bond with D271. This sulfur could mimic a carbonyl oxygen in the backbone of a peptide, suggesting a possible substrate binding mechanism.
+Binding of PBD150 to DromeQC utilizes π-π, arene-H, and hydrogen bonding interactions (Figure 4). The dimethoxyphenyl phenyl group of PBD150 is stabilized by π-π interactions with F292. This phenyl group is highly flexibily, however, as only weak electron density was observed during crystal structure analysis. Such flexibility could be essential for substrates to cyclize. Also stabilizing the inhibitor is an arene-H interaction made between the imidazole moiety of PBD150 and W296. The first carbon upstream of this imidazole ring forms an additional arene-H contact with W176. Finally, the sulfur contained in the thiourea group makes a hydrogen bond with D271. This sulfur could mimic a carbonyl oxygen in the backbone of a peptide, suggesting a possible substrate binding mechanism.
 ==Function==