Graph-representation of oxidative folding pathways

Ágoston, Vilmos; Cemazar, Masa; Kaján, László; Pongor, Sándor

doi:10.1186/1471-2105-6-19

Cited by 7 publications

(2 citation statements)

References 31 publications

(22 reference statements)

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“…This is in good accordance with the general view that local interactions dominate the first stages of protein folding. In order to get insights into the role the intermediates we prepared a folding map with intermediates as the nodes and disulfide exchange reactions as the edges (Agoston et al, 2005). The logics underlying this representation is that fully oxidized intermediates such as observed for AAI can undergo intramolecular disulfide interchange reactions that rewire the two participating disulfide bridges (example shown in Figure 6).…”

Section: Synthesis and In Vitro Oxidative Folding Of Aaimentioning

confidence: 99%

Structure and Oxidative Folding of AAI, the Major Alfa-Amylase Inhibitor From Amaranth Seeds

2020

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AAI, the major alpha-amylase inhibitor (AAI) present in the seeds of the Mexican crop plant Amaranthus hypocondriacus is a 32-residue-long polypeptide with three disulfide bridges. Its structure is most closely related to the plant amylase inhibitor subfamily of knottins characterized by a topological knot formed by one disulfide bridge threading through a loop formed by the peptide chain as well as a short three-stranded beta sandwich core. AAI is specific against insect amylases and does not act on corresponding human or mammalian enzymes. It was found that the oxidative folding of AAI seems to follow a hirudine-like pathway with many non-native intermediates, but notably it proceeds through a major folding intermediate (MFI) that contains a vicinal disulfide bridge. Based on a review of the pertinent literature, the known vicinal disulfides in native proteins as well as well as the network of disulfide interchanges, we propose that MFI is a kinetic trap corresponding to a compact molten globule-like state which constrains the peptide chain to a smaller number of conformations that in turn can be rapidly funneled toward the native state. AAI: THE MAJOR ALPHA AMYLASE INHIBITOR OF Amaranthus hypochondriacusAAI (amaranth amylase inhibitor) is an alpha-amylase inhibitor isolated from the Mexican crop plant Amaranthus hypochondriacus. Amaranth grains are known to be cultivated for about 8,000 years and were part of the diet of the Aztecs. Today, Amaranth is grown in Mexico, Peru, and Bolivia, but the world's largest producer is China with an estimated annual production of 87 million metric tons. Amaranths are classified as pseudo cereals as they are not in the same botanical family as true cereals to which their grains bear similarity.Aqueous extracts of Amaranth grains were found to inhibit insect alpha-amylases extracted from the larvae of the red flour beetle (Dibolium castaneum) and of the grain borer (Prostephanus truncatus). The alpha-amylase was purified with classical techniques (Chagolla-Lopez et al., 1994). Briefly, crude extracts of amaranth flour were fractionated by ammonium sulfate precipitation (35-65%), fractionated on G75 Sepharose columns and the lyophilized active fractions were subjected to ion exchange chromatography The majority of inhibitory activity was found in one major peak which was further purified with reverse phase HPLC (RP-HPLC). The inhibitory activity was resistant to heat. As amino acid analysis revealed a high percentage of cysteine with no free sulfhydryl groups, the samples were reduced

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Section: Synthesis and In Vitro Oxidative Folding Of Aaimentioning

confidence: 99%

Structure and Oxidative Folding of AAI, the Major Alfa-Amylase Inhibitor From Amaranth Seeds

2020

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“…The similarity group is a group of molecules that share a well-defined type of similarity [66]. This similarity can be local or global, structural or functional etc.…”

Section: Similarity Groupsmentioning

confidence: 99%

Detecting Atypical Examples of Known Domain Types by Sequence Similarity Searching: The SBASE Domain Library Approach

Dhir¹,

Pacurar²,

Franklin³

et al. 2010

CPPS

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SBASE is a project initiated to detect known domain types and predicting domain architectures using sequence similarity searching (Simon et al., Protein Seq Data Anal, 5: 39-42, 1992, Pongor et al., Nucl. Acids. Res. 21:3111-3115, 1992. The current approach uses a curated collection of domain sequences -the SBASE domain library -and standard similarity search algorithms, followed by postprocessing which is based on a simple statistics of the domain similarity network (http://hydra.icgeb.trieste.it/sbase/). It is especially useful in detecting rare, atypical examples of known domain types which are sometimes missed even by more sophisticated methodologies. This approach does not require multiple alignment or machine learning techniques, and can be a useful complement to other domain detection methodologies. This article gives an overview of the project history as well as of the concepts and principles developed within this the project.

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Cooperation between a Salt Bridge and the Hydrophobic Core Triggers Fold Stabilization in a Trp-Cage Miniprotein

et al. 2007

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Miniproteins are adequate models to study various protein-structure modifying effects such as temperature, pH, point mutation(s), H-bonds, salt bridges, molecular packing, etc. Tc5b, a 20-residue Trp-cage protein is one of the smallest of such models with a stable 3D fold (Neidigh J. W. et al. (2002) Nat. Struct. Biol. 9, 425-430). However, Tc5b exhibits considerable heat-sensitivity and is only stable at relatively low temperatures. Here we report a systematic investigation of structural factors influencing the stability of Tc5b by solving its solution structure in different environments, varying temperature, and pH. The key interactions identified are the hydrophobic stacking of the aromatic rings of Tyr3 and Trp6 and the salt bridge formed between Asp9 and Arg18. To verify the importance of these interactions, selected variants (mutated, glycosylated and truncated) of Tc5b were designed, prepared, and investigated by NMR. Indeed, elimination of either of the key interactions highly destabilizes the structure. These observations enabled us to design a new variant, Tc6b, differing only by a methylene group from Tc5b, in which both key interactions are optimized simultaneously. Tc6b exhibits enhanced heat stability and adopts a stable fold at physiological temperature.

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Graph-representation of oxidative folding pathways

Cited by 7 publications

References 31 publications

Structure and Oxidative Folding of AAI, the Major Alfa-Amylase Inhibitor From Amaranth Seeds

Structure and Oxidative Folding of AAI, the Major Alfa-Amylase Inhibitor From Amaranth Seeds

Detecting Atypical Examples of Known Domain Types by Sequence Similarity Searching: The SBASE Domain Library Approach

Cooperation between a Salt Bridge and the Hydrophobic Core Triggers Fold Stabilization in a Trp-Cage Miniprotein

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