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Towards a Pharmacophore for Amyloid
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نویسنده
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landau m. ,sawaya m.r. ,faull k.f. ,laganowsky a. ,jiang l. ,sievers s.a. ,liu j. ,barrio j.r. ,eisenberg d.
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منبع
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plos biology - 2011 - دوره : 9 - شماره : 6
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چکیده
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Diagnosing and treating alzheimer's and other diseases associated with amyloid fibers remains a great challenge despite intensive research. to aid in this effort,we present atomic structures of fiber-forming segments of proteins involved in alzheimer's disease in complex with small molecule binders,determined by x-ray microcrystallography. the fiber-like complexes consist of pairs of β-sheets,with small molecules binding between the sheets,roughly parallel to the fiber axis. the structures suggest that apolar molecules drift along the fiber,consistent with the observation of nonspecific binding to a variety of amyloid proteins. in contrast,negatively charged orange-g binds specifically to lysine side chains of adjacent sheets. these structures provide molecular frameworks for the design of diagnostics and drugs for protein aggregation diseases. © 2011 landau et al.
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آدرس
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howard hughes medical institute,ucla-doe institute for genomics and proteomics,departments of biological chemistry and chemistry and biochemistry,university of california,los angeles,ca, United States, howard hughes medical institute,ucla-doe institute for genomics and proteomics,departments of biological chemistry and chemistry and biochemistry,university of california,los angeles,ca, United States, the pasarow mass spectrometry laboratory,the npi-semel institute for neuroscience and human behavior,david geffen school of medicine,university of california,los angeles,ca, United States, howard hughes medical institute,ucla-doe institute for genomics and proteomics,departments of biological chemistry and chemistry and biochemistry,university of california,los angeles,ca, United States, howard hughes medical institute,ucla-doe institute for genomics and proteomics,departments of biological chemistry and chemistry and biochemistry,university of california,los angeles,ca, United States, howard hughes medical institute,ucla-doe institute for genomics and proteomics,departments of biological chemistry and chemistry and biochemistry,university of california,los angeles,ca, United States, department of molecular and medical pharmacology,david geffen school of medicine,university of california,los angeles,ca, United States, department of molecular and medical pharmacology,david geffen school of medicine,university of california,los angeles,ca, United States, howard hughes medical institute,ucla-doe institute for genomics and proteomics,departments of biological chemistry and chemistry and biochemistry,university of california,los angeles,ca, United States
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Authors
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