3T4G

AIIGLMV segment from Alzheimer's Amyloid-Beta displayed on 54-membered macrocycle scaffold

Summary for 3T4G

• Entry DOI: 10.2210/pdb3t4g/pdb
• Descriptor: Cyclic pseudo-peptide (ORN)AIIGLMV(ORN)KF(HAO)(4BF)K, (4S)-2-METHYL-2,4-PENTANEDIOL (2 entities in total)
• Functional Keywords: amyloid-related, macrocycle, hao, unknown function
• Total number of polymer chains: 2
• Total formula weight: 4212.94

Authors

Zhao, M.,Liu, C.,Cheng, P.N.,Eisenberg, D.,Nowick, J.S. (deposition date: 2011-07-26, release date: 2012-10-31, Last modification date: 2023-11-15)

Primary citation

Cheng, P.N.,Liu, C.,Zhao, M.,Eisenberg, D.,Nowick, J.S.
Amyloid beta-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity.
Nat Chem, 4:927-933, 2012

PubMed Abstract: The amyloid protein aggregation associated with diseases such as Alzheimer's, Parkinson's and type II diabetes (among many others) features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibres. The variation in the amino-acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. Here, we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize the aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from the amyloid-β peptide associated with Alzheimer's disease, β(2)-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson's disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles.

PubMed: 23089868
DOI: 10.1038/nchem.1433

Experimental method

X-RAY DIFFRACTION (1.7 Å)