Sandbox Reserved 1620: Difference between revisions
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==Disease== | ==Disease== | ||
[[Image:Ligand_Interactions_6ffc.png|400 px|right|thumb|Figure 3: MZ29 bound to cavity 1 of ABCG2 [https://www.rcsb.org/structure/6FFC (6FFC)]. Two MZ29 are shown in sticks and are colored by element. Hydrophobic interactions between the surface of cavity 1 and MZ29 are shown in green.]] | [[Image:Ligand_Interactions_6ffc.png|400 px|right|thumb|Figure 3: MZ29 bound to cavity 1 of ABCG2 [https://www.rcsb.org/structure/6FFC (6FFC)]. Two MZ29 are shown in sticks and are colored by element. Hydrophobic interactions between the surface of cavity 1 and MZ29 are shown in green.]] | ||
Dysfunctions in ABCG2 are linked to [https://en.wikipedia.org/wiki/Hyperuricemia hyperuricemia] which can lead to [https://en.wikipedia.org/wiki/Gout gout], [https://en.wikipedia.org/wiki/Kidney_disease kidney disease], and [https://en.wikipedia.org/wiki/Hypertension hypertension], all of which are thought to be the result of impaired transport of uric acid. Additionally, the expression of ABCG2 has been found to correlate with a poor prognosis and treatment outcome of various cancers including breast, ovarian, and lung.<ref name="Jackson"/> | Dysfunctions in ABCG2 are linked to [https://en.wikipedia.org/wiki/Hyperuricemia hyperuricemia] which can lead to [https://en.wikipedia.org/wiki/Gout gout], [https://en.wikipedia.org/wiki/Kidney_disease kidney disease], and [https://en.wikipedia.org/wiki/Hypertension hypertension], all of which are thought to be the result of impaired transport of uric acid. Additionally, the expression of ABCG2 has been found to correlate with a poor prognosis and treatment outcome of various cancers including breast, ovarian, and lung.<ref name="Jackson">PMID:29610494</ref> | ||
Several mutations also decrease transporter activity.<ref name="Taylor"/><ref name="Manolaridis"/><ref name="Robey"/> The most detrimental of these is a point mutation of <scene name='83/832939/Residue_211/1'>Glu211 to Gln211</scene> , which completely abolished activity of the transporter. Another point mutation occurs <scene name='83/832939/The_cause_of_gout/1'>at Gln141</scene>, which when mutated to lysine causes gout by distorting ABCG2's tertiary structure. Changes at <scene name='83/832939/R482/1'>Arg482</scene> shift the substrate specificity of ABCG2 by [https://en.wikipedia.org/wiki/Allosteric_regulation allosteric effects] as this residue is distantly located from the binding pocket. | Several mutations also decrease transporter activity.<ref name="Taylor"/><ref name="Manolaridis"/><ref name="Robey"/> The most detrimental of these is a point mutation of <scene name='83/832939/Residue_211/1'>Glu211 to Gln211</scene> , which completely abolished activity of the transporter. Another point mutation occurs <scene name='83/832939/The_cause_of_gout/1'>at Gln141</scene>, which when mutated to lysine causes gout by distorting ABCG2's tertiary structure. Changes at <scene name='83/832939/R482/1'>Arg482</scene> shift the substrate specificity of ABCG2 by [https://en.wikipedia.org/wiki/Allosteric_regulation allosteric effects] as this residue is distantly located from the binding pocket. | ||
