Sandbox Reserved 1661: Difference between revisions

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Somatotropin does not exist as a linear chain of amino acids, it twists and folds on itself, forming the '''secondary structure'''. The protein, made up of a single chain, consists of four antiparallel aligned <scene name='86/868194/Alpha-helice/1'>α-helices</scene> in an up-up-down-down manner <ref name="Endokrynologika Polska">DOI:10.5603/EP.2013.0009</ref> [https://doi.org/10.1016/j.ghir.2013.02.002]. The first helix starts at the 6th amino acid, which is a leucine and ends with the 37th amino acid proline. It is separated from the other three helices after the 37th position. The 38th and 39th amino acids, which are lysine and glutamic acid are spliced out of the protein and therefore disconnects the first helix from the second one. The second helix starts at position 72 till 92, the third from 106 till 128 and the fourth helix from 154 until 184. All helices are ampipathic with strong <scene name='86/868194/Hydrophobic_regions/1'>hydrophobic regions</scene>, especially helix 2 is very hydrophobic. The [https://en.wikipedia.org/wiki/Hydrophobic_effect#:~:text=Structures%20of%20water%2Dsoluble%20proteins,interact%20with%20surrounding%20water%20molecules. hydrophobic protein core] is usually tigthly packed and any mutations in the hidden positions lead to destablilization <ref name="pubMed">PMID:17584122</ref>.

From the secondary structure, we obtain the '''tertiary structure''', which corresponds to the 3D structure adopted by all the alpha helixes. The structural maintenance is stabilised by electrostatic, hydrophobic and polar interactions, <scene name='86/868194/Lh/1'>hydrogen bonds</scene> and/or covalent interactions with [https://en.wikipedia.org/wiki/Cysteine cysteine] 53 and cysteine 165 that form a <scene name='86/868194/Pds/2'>disulphide bridge</scene> as well as cysteine 182 with cysteine 189 [https://www.rcsb.org/3d-view/1HGU]. Cys53 and C165 also link the crossover connection between helices 1 and 2 to helix 4. The other cysteine-pair form a small loop in C-terminus, involved in the receptor binding site 1 with direct contact to the extracellular domain of the GH receptor [https://doi.org/10.1016/j.ghir.2013.02.002]. It is also requiried for stability, but unlike the first cysteine-pair not essential for biological activity <ref name="Endokrynologika Polska">DOI:10.5603/EP.2013.0009</ref>. A disruption of these disulphide bridges drastically reduces the molecule stability, but only if one unpaired cysteine remains intact. This may lead to implifications for diagnosis or treatments of growth disorder [https://doi.org/10.1016/j.ghir.2013.02.002].

From the secondary structure, we obtain the '''tertiary structure''', which corresponds to the 3D structure adopted by all the alpha helixes. The structural maintenance is stabilised by electrostatic, hydrophobic and polar interactions, <scene name='86/868194/Lh/1'>hydrogen bonds</scene> and/or covalent interactions with [https://en.wikipedia.org/wiki/Cysteine cysteine] 53 and cysteine 165 that form a <scene name='86/868194/Pds/1'>disulphide bridge</scene> as well as cysteine 182 with cysteine 189 [https://www.rcsb.org/3d-view/1HGU]. Cys53 and C165 also link the crossover connection between helices 1 and 2 to helix 4. The other cysteine-pair form a small loop in C-terminus, involved in the receptor binding site 1 with direct contact to the extracellular domain of the GH receptor [https://doi.org/10.1016/j.ghir.2013.02.002]. It is also requiried for stability, but unlike the first cysteine-pair not essential for biological activity <ref name="Endokrynologika Polska">DOI:10.5603/EP.2013.0009</ref>. A disruption of these disulphide bridges drastically reduces the molecule stability, but only if one unpaired cysteine remains intact. This may lead to implifications for diagnosis or treatments of growth disorder [https://doi.org/10.1016/j.ghir.2013.02.002].

The protein has two different binding sites: both located at the ends of the protein, the N-terminus as well as the C-terminus [https://edoc.ub.uni-muenchen.de/8706/1/Burget_Lukas.pdf].

The GH consists of two hydrophobic cores, one is composed of Trp104 (hGH-receptor1), Trp169 (hGH-receptor1), Pro61 (hGH), Phe176 (hGH) and Ile176 (hGH). Especially Pro61 is important, it is involved in the formation of the ative conformation of hydrophobic core amino acids and interacting with other hydrophobic core amino acids within 5Å. A mutation in this point leads to a decrease of biological and receptor binding activity. The other one is composed of two pairs of interaction between Trp76 (hGH-receptor1) and Pro48 (hGH) and between Pro106 (hGH-receptor1) and Leu45 (hGH). <ref name="pubMed">PMID:17584122</ref>

Sandbox Reserved 1661: Difference between revisions

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@@ Line 15: / Line 15: @@
 Somatotropin does not exist as a linear chain of amino acids, it twists and folds on itself, forming the '''secondary structure'''. The protein, made up of a single chain, consists of four antiparallel aligned <scene name='86/868194/Alpha-helice/1'>α-helices</scene> in an up-up-down-down manner <ref name="Endokrynologika Polska">DOI:10.5603/EP.2013.0009</ref> [https://doi.org/10.1016/j.ghir.2013.02.002]. The first helix starts at the 6th amino acid, which is a leucine and ends with the 37th amino acid proline. It is separated from the other three helices after the 37th position. The 38th and 39th amino acids, which are lysine and glutamic acid are spliced out of the protein and therefore disconnects the first helix from the second one. The second helix starts at position 72 till 92, the third from 106 till 128 and the fourth helix from 154 until 184. All helices are ampipathic with strong <scene name='86/868194/Hydrophobic_regions/1'>hydrophobic regions</scene>, especially helix 2 is very hydrophobic. The [https://en.wikipedia.org/wiki/Hydrophobic_effect#:~:text=Structures%20of%20water%2Dsoluble%20proteins,interact%20with%20surrounding%20water%20molecules. hydrophobic protein core] is usually tigthly packed and any mutations in the hidden positions lead to destablilization <ref name="pubMed">PMID:17584122</ref>.
-From the secondary structure, we obtain the '''tertiary structure''', which corresponds to the 3D structure adopted by all the alpha helixes. The structural maintenance is stabilised by electrostatic, hydrophobic and polar interactions, <scene name='86/868194/Lh/1'>hydrogen bonds</scene> and/or covalent interactions with [https://en.wikipedia.org/wiki/Cysteine cysteine] 53 and cysteine 165 that form a <scene name='86/868194/Pds/2'>disulphide bridge</scene> as well as cysteine 182 with cysteine 189 [https://www.rcsb.org/3d-view/1HGU]. Cys53 and C165 also link the crossover connection between helices 1 and 2 to helix 4. The other cysteine-pair form a small loop in C-terminus, involved in the receptor binding site 1 with direct contact to the extracellular domain of the GH receptor [https://doi.org/10.1016/j.ghir.2013.02.002]. It is also requiried for stability, but unlike the first cysteine-pair not essential for biological activity <ref name="Endokrynologika Polska">DOI:10.5603/EP.2013.0009</ref>. A disruption of these disulphide bridges drastically reduces the molecule stability, but only if one unpaired cysteine remains intact. This may lead to implifications for diagnosis or treatments of growth disorder [https://doi.org/10.1016/j.ghir.2013.02.002].
+From the secondary structure, we obtain the '''tertiary structure''', which corresponds to the 3D structure adopted by all the alpha helixes. The structural maintenance is stabilised by electrostatic, hydrophobic and polar interactions, <scene name='86/868194/Lh/1'>hydrogen bonds</scene> and/or covalent interactions with [https://en.wikipedia.org/wiki/Cysteine cysteine] 53 and cysteine 165 that form a <scene name='86/868194/Pds/1'>disulphide bridge</scene> as well as cysteine 182 with cysteine 189 [https://www.rcsb.org/3d-view/1HGU]. Cys53 and C165 also link the crossover connection between helices 1 and 2 to helix 4. The other cysteine-pair form a small loop in C-terminus, involved in the receptor binding site 1 with direct contact to the extracellular domain of the GH receptor [https://doi.org/10.1016/j.ghir.2013.02.002]. It is also requiried for stability, but unlike the first cysteine-pair not essential for biological activity <ref name="Endokrynologika Polska">DOI:10.5603/EP.2013.0009</ref>. A disruption of these disulphide bridges drastically reduces the molecule stability, but only if one unpaired cysteine remains intact. This may lead to implifications for diagnosis or treatments of growth disorder [https://doi.org/10.1016/j.ghir.2013.02.002].
 The protein has two different binding sites: both located at the ends of the protein, the N-terminus as well as the C-terminus [https://edoc.ub.uni-muenchen.de/8706/1/Burget_Lukas.pdf].
 The GH consists of two hydrophobic cores, one is composed of Trp104 (hGH-receptor1), Trp169 (hGH-receptor1), Pro61 (hGH), Phe176 (hGH) and Ile176 (hGH). Especially Pro61 is important, it is involved in the formation of the ative conformation of hydrophobic core amino acids and interacting with other hydrophobic core amino acids within 5Å. A mutation in this point leads to a decrease of biological and receptor binding activity. The other one is composed of two pairs of interaction between Trp76 (hGH-receptor1) and Pro48 (hGH) and between Pro106 (hGH-receptor1) and Leu45 (hGH). <ref name="pubMed">PMID:17584122</ref>