Evolutionary Traits of Toxins

Kumar, Raj; Chang, Tzuu-Wang; Singh, Bal Ram

doi:10.1007/978-94-007-5869-8_29

Cited by 4 publications

(5 citation statements)

References 50 publications

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“…Therefore, this hypothesis provides a common thread running through diverse phenomena [168]. Interestingly enough, later work has confirmed that functionally relevant unfolded structures of many bacterial toxins are molten globules [221][222][223].…”

Section: Molten Globules and Intrinsic Disorder In Proteinsmentioning

confidence: 82%

Pre-Molten, Wet, and Dry Molten Globules en Route to the Functional State of Proteins

Gupta

Uversky

2023

IJMS

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Transitions between the unfolded and native states of the ordered globular proteins are accompanied by the accumulation of several intermediates, such as pre-molten globules, wet molten globules, and dry molten globules. Structurally equivalent conformations can serve as native functional states of intrinsically disordered proteins. This overview captures the characteristics and importance of these molten globules in both structured and intrinsically disordered proteins. It also discusses examples of engineered molten globules. The formation of these intermediates under conditions of macromolecular crowding and their interactions with nanomaterials are also reviewed.

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Section: Molten Globules and Intrinsic Disorder In Proteinsmentioning

confidence: 82%

Pre-Molten, Wet, and Dry Molten Globules en Route to the Functional State of Proteins

Gupta

Uversky

2023

IJMS

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“…Analyzing their sequences and study of their function suggest that the ancestor of neurotoxins may not be in Clostridium genus, but rather may have been from viral polyproteins [124]. Alternatively, as highlighted by Kumar et al [125] that although there is very little similarity in the sequence outside the Clostridial Neurotoxin (CNT) family, it is possible to find an evolutionary correlation by establishing the relationship with similar structural and functional domains. Thus, two possibilities of BoNTs evolution are: BoNTs either evolved from a family of BoNT-like toxins, or BoNT genes may have spread to other organisms through HGT.…”

Section: Evolution Of Bacterial Toxinsmentioning

confidence: 99%

“…This suggests that the substrates are not necessarily limited to SNARE proteins from vertebrate for clostridial neurotoxins. The co-evolution of substrate and toxins could play a role in the unique specificity of clostridial neurotoxins [125,133]. Chang and Singh [133] established the phenogram of different serotypes and their subtypes of clostridial neurotoxins, suggesting that BoNT/E is farthest (the least sequence convergence) from BoNT/C and /D (the most sequence convergence), while BoNT/A and TeNT is in between (Figure 3; [133] Further analysis of the substrates of BoNT/A, /C, and /E (SNAP-25 and syntaxin) revealed that the BoNT/E cleavage site has the highest sequence conservation, while the cleavage site of type C has the least conservation, inversely correlating with the phenetic tree of BoNTs [125,133].…”

Section: Evolution Of Bacterial Toxinsmentioning

confidence: 99%

“…Evolution is one of the greatest discoveries and widely debated topic in science. A few schools of thought hypothesized several possibilities for the origin of life [125], but the original primordial organism is missing in all current theories, it is “unknowable” and scientifically far from having definition. A root of any phenotypic tree is characterized as the most common ancestor, which is unknown.…”

Section: Evolution Of Bacterial Toxinsmentioning

confidence: 99%

“…This will allow us to investigate the correlation between the target molecule and its possible interactions. Chang, Kumar, and Singh [125] employed a similar strategy to establish the correlation between botulinum toxin and its substrate. Entropy is a fundamental concept, however, and using this concept with biological molecules is a double-edged sword.…”

Section: Evolution Of Bacterial Toxinsmentioning

confidence: 99%

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Evolutionary Features in the Structure and Function of Bacterial Toxins

Kumar

Feltrup

Kukreja

et al. 2019

Toxins

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Toxins can function both as a harmful and therapeutic molecule, depending on their concentrations. The diversity in their function allows us to ask some very pertinent questions related to their origin and roles: (a) What makes them such effective molecules? (b) Are there evolutionary features encoded within the structures of the toxins for their function? (c) Is structural hierarchy in the toxins important for maintaining their structure and function? (d) Do protein dynamics play a role in the function of toxins? and (e) Do the evolutionary connections to these unique features and functions provide the fundamental points in driving evolution? In light of the growing evidence in structural biology, it would be appropriate to suggest that protein dynamics and flexibility play a much bigger role in the function of the toxin than the structure itself. Discovery of IDPs (intrinsically disorder proteins), multifunctionality, and the concept of native aggregation are shaking the paradigm of the requirement of a fixed three-dimensional structure for the protein’s function. Growing evidence supporting the above concepts allow us to redesign the structure-function aspects of the protein molecules. An evolutionary model is necessary and needs to be developed to study these important aspects. The criteria for a well-defined model would be: (a) diversity in structure and function, (b) unique functionality, and (c) must belong to a family to define the evolutionary relationships. All these characteristics are largely fulfilled by bacterial toxins. Bacterial toxins are diverse and widely distributed in all three forms of life (Bacteria, Archaea and Eukaryotes). Some of the unique characteristics include structural folding, sequence and functional combination of domains, targeting a cellular process to execute their function, and most importantly their flexibility and dynamics. In this work, we summarize certain unique aspects of bacterial toxins, including role of structure in defining toxin function, uniqueness in their enzymatic function, and interaction with their substrates and other proteins. Finally, we have discussed the evolutionary aspects of toxins in detail, which will help us rethink the current evolutionary theories. A careful study, and appropriate interpretations, will provide answers to several questions related to the structure-function relationship of proteins, in general. Additionally, this will also allow us to refine the current evolution theories.

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Evolution of Toxin

Kumar¹,

Singh²

2016

SpringerBriefs in Biochemistry and Molecular Biology

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Evolutionary Traits of Toxins

Cited by 4 publications

References 50 publications

Pre-Molten, Wet, and Dry Molten Globules en Route to the Functional State of Proteins

Pre-Molten, Wet, and Dry Molten Globules en Route to the Functional State of Proteins

Evolutionary Features in the Structure and Function of Bacterial Toxins

Evolution of Toxin

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