Related Experiment Video
Updated: Jun 27, 2025
05:48
Rapid Generation of Amyloid from Native Proteins In vitro
Published on: December 5, 2013
6.2K
Catalysis driven by an amyloid-substrate complex
Taka Sawazaki1, Daisuke Sasaki1, Youhei Sohma1
1Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama 640-8156, Japan.
Summary
A novel amyloid catalyst system (CASL) activates ammonium ions for amine modification reactions under acidic conditions. This breakthrough enables common chemical transformations previously hindered by low pH.
Area of Science:
- Chemical Biology
- Organic Chemistry
- Biocatalysis
Background:
- Amine modification is crucial in chemistry and biology.
- Alkyl amines are poorly nucleophilic in acidic buffers due to ammonium ion formation.
- Existing methods struggle with amine modification under acidic, biorelevant conditions.
Purpose of the Study:
- To develop a novel catalytic system for amine modification in acidic buffer.
- To overcome the limitations of ammonium ion nucleophilicity at acidic pH.
- To demonstrate the versatility of amyloid catalysts in promoting amine transformations.
Main Methods:
- Development of a catalysis driven by amyloid-substrate complex (CASL) system.
- Utilizing a specific amyloid catalyst (NL6) derived from islet amyloid polypeptide (IAPP).
- Employing crystallographic analysis and chemical modification studies to elucidate the catalytic mechanism.
Main Results:
- CASL effectively promotes various amine modifications (acylation, arylation, cyclization, alkylation) in acidic buffer.
- The carbonyl oxygen of the Phe-Gly amide bond in NL6 is key for activating substrate amines via hydrogen bonding.
- Selective conversion of substrates with similar amine reactivity was achieved using amyloid catalysts.
- Demonstrated the utility of CASL for amine modifications under acidic conditions.
Conclusions:
- CASL represents a unique molecular transformation system for amine modification.
- Amyloid catalysts can activate ammonium ions, enabling reactions previously difficult at acidic pH.
- This method offers a new approach for amine functionalization in chemistry and biology.
Related Concept Videos
03:03Amyloid Fibrils
9.5K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.5K
02:41Protein Complex Assembly
10.6K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.6K
01:13Introduction to Mechanisms of Enzyme Catalysis
8.1K
For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes...
8.1K
02:34Enzymes
81.5K
Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
81.5K
01:48ATP Synthase: Mechanism
14.5K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.5K
01:19Allosteric Proteins-ATCase
5.7K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.7K