Journal ArticleDOI
Basic units of protein structure, folding, and function
TLDR
It is shown how evolutionary relations between protein functional superfamilies and folds delineated with the help of EFLs can contribute to establishing the rules for design of desired enzymatic functions.Abstract:
Study of the hierarchy of domain structure with alternative sets of domains and analysis of discontinuous domains, consisting of remote segments of the polypeptide chain, raised a question about the minimal structural unit of the protein domain. The hypothesis on the decisive role of the polypeptide backbone in determining the elementary units of globular proteins have led to the discovery of closed loops. It is reviewed here how closed loops form the loop-n-lock structure of proteins, providing the foundation for stability and designability of protein folds/domain and underlying their co-translational folding. Simplified protein sequences are considered here with the aim to explore the basic principles that presumably dominated the folding and stability of proteins in the early stages of structural evolution. Elementary functional loops (EFLs), closed loops with one or few catalytic residues, are, in turn, units of the protein function. They are apparent descendants of the prebiotic ring-like peptides, which gave rise to the first functional folds/domains being fused in the beginning of the evolution of protein structure. It is also shown how evolutionary relations between protein functional superfamilies and folds delineated with the help of EFLs can contribute to establishing the rules for design of desired enzymatic functions. Generalized descriptors of the elementary functions are proposed to be used as basic units in the future computational design.read more
Citations
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Computing disease-linked SOD1 mutations: deciphering protein stability and patient-phenotype relations.
Vijay Kumar,Safikur Rahman,Hani Choudhry,Mazin A. Zamzami,Mohammad Sarwar Jamal,Asimul Islam,Faizan Ahmad,Md. Imtaiyaz Hassan +7 more
TL;DR: Correlation between disease phenotypes and stability changes suggest that the changes in SOD1 stability correlate with ALS patient survival times, demonstrating the importance of protein stability in S OD1 pathogenicity.
Journal ArticleDOI
Predicting changes to I Na from missense mutations in human SCN5A
TL;DR: It is shown that changes to INa, the mechanism through which SCN5A mutations create cardiac risk, are already difficult to predict using purely in-silico methods, and underscores the need for functional studies of INa in risk assessment.
Journal ArticleDOI
Evolution, folding, and design of TIM barrels and related proteins.
TL;DR: In-depth sequence analysis reveals that the protein fold universe is more evolutionarily connected than previously assumed and is a model system to explore evolution, folding, and design.
Journal ArticleDOI
Evolution of networks of protein domain organization.
TL;DR: These networks revealed two ancient waves of structural novelty arising from ancient ‘p-loop’ and ‘winged helix’ domains and a massive ‘big bang’ of domain organization, and highlighted a central evolutionary role of cofactor-supporting structures of non-ribosomal peptide pathways in NRPS pathways.
Journal ArticleDOI
The Effect of (-)-Epigallocatechin-3-Gallate Non-Covalent Interaction with the Glycosylated Protein on the Emulsion Property.
TL;DR: After the addition of EGCG, the mean particle size of emulsions decreased with the increasing absolute value of zeta-potential, and more compact interfacial film was formed due to the higher percentage of interfacial protein adsorption (AP%).
References
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Journal ArticleDOI
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Helen M. Berman,John D. Westbrook,Zukang Feng,Gary L. Gilliland,Talapady N. Bhat,Helge Weissig,Ilya N. Shindyalov,Philip E. Bourne +7 more
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Journal ArticleDOI
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Journal ArticleDOI
Dominant forces in protein folding
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