Hot spots-A review of the protein-protein interface determinant amino-acid residues

2007 ◽  
Vol 68 (4) ◽  
pp. 803-812 ◽  
Author(s):  
Irina S. Moreira ◽  
Pedro A. Fernandes ◽  
Maria J. Ramos
Keyword(s):  
Amino Acid ◽  
Hot Spots ◽  
Amino Acid Residues ◽  
Protein Interface

scholarly journals Insulin Hot-Spot Analogs Formed with N-Methylated Amino Acid Residues Inhibit Aggregation of Native Hormone

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3706 ◽  
Author(s):  
Swiontek ◽  
Wasko ◽  
Fraczyk ◽  
Galecki ◽  
Kaminski ◽  
...  
Keyword(s):  
Amino Acid ◽  
Hot Spots ◽  
Solid Phase ◽  
Hot Spot ◽  
Amino Acid Residues ◽  
Native Conformation ◽  
Hormone Synthesis ◽  
Coupling Reagent ◽  
Aggregation Processes ◽  
Lower Ability

In this study, N-methylated analogs of hot-spots of insulin were designed and synthesized, in the expectation that they would inhibit the aggregation of both insulin hot-spots and the entire hormone. Synthesis of insulin “amyloidogenic” analogs containing N-methylated amino acid residues was performed by microwave-assisted solid phase according to the Fmoc/tert-Bu strategy. As a coupling reagent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TosO-) was used. Three independent methods were applied in aggregation studies of the complexes of insulin with its N-methylated peptides. Additionally, circular dichroism (CD) measurements were used to confirm that aggregation processes did not occur in the presence of the N-methylated analogs of hot-spot insulin fragments, and that insulin retains its native conformation. Of the seven N-methylated analogs of the A- and B-chain hot-spots of insulin, six inhibited insulin aggregation (peptides 1 and 3–7). All tested peptides were found to have a lower ability to inhibit the aggregation of insulin hot-spots compared to the capability to inhibit native hormone aggregation.

scholarly journals Prediction of amyloidogenicity based on the n-gram analysis

2016 ◽  
Author(s):  
Michał Jan Burdukiewicz ◽  
Piotr Sobczyk ◽  
Stefan Rödiger ◽  
Anna Duda-Madej ◽  
Paweł Mackiewicz ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Hot Spots ◽  
Permutation Test ◽  
Strongly Correlated ◽  
Amino Acid Residues ◽  
Data Set ◽  
Amyloid Peptides ◽  
External Data ◽  
N Gram

Amyloids are proteins associated with the number of clinical disorders (e.g., Alzheimer's, Creutzfeldt-Jakob's and Huntington's diseases). Despite their diversity, all amyloid proteins can undergo aggregation initiated by 6- to 15-residue segments, called hot spots. To find the patterns defining the hot-spots, we trained predictors of amyloidogenicity, using n-grams and random forest classifiers, based on data collected in the AmyLoad database. Only the most informative n-grams, selected by our Quick Permutation Test, were considered. Since the amyloidogenicity may not depend on the exact sequence of amino acids but on more general properties of amino acids, we tested 524,284 reduced amino acid alphabets of different lengths (three to six letters) to find the alphabet providing the best performance in cross-validation. The predictor based on this alphabet, called AmyloGram, was benchmarked against the most popular tools for the detection of amyloid peptides using an external data set and obtained the highest values of performance measures (AUC: 0.90, MCC: 0.63). Our results showed sequential patterns in the amyloids, which are strongly correlated with hydrophobicity, a tendency to form ß-sheets and rigidity of amino acid residues. Among the most informative n-grams of AmyloGram we identified 15 that were already confirmed experimentally. AmyloGram is available as a web-server: www.smorfland.uni.wroc.pl/amylogram/. The code and results are publicly available at: www.github.com/michbur/prediction_amyloidogenicity_ngram/.

scholarly journals Intrinsic Disorder-Based Design of Stable Globular Proteins

Biomolecules ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 64 ◽  
Author(s):  
Galina S. Nagibina ◽  
Ksenia A. Glukhova ◽  
Vladimir N. Uversky ◽  
Tatiana N. Melnik ◽  
Bogdan S. Melnik
Keyword(s):  
Amino Acid ◽  
Hot Spots ◽  
Point Mutations ◽  
Intrinsic Disorder ◽  
Query Protein ◽  
Globular Proteins ◽  
Amino Acid Residues ◽  
Weak Spot ◽  
Stable Mutant ◽  
Mutant Forms

Directed stabilization of globular proteins via substitution of a minimal number of amino acid residues is one of the most complicated experimental tasks. This work summarizes our research on the effect of amino acid substitutions on the protein stability utilizing the outputs of the analysis of intrinsic disorder predisposition of target proteins. This allowed us to formulate the basis of one of the possible approaches to the stabilization of globular proteins. The idea is quite simple. To stabilize a protein as a whole, one needs to find its "weakest spot" and stabilize it, but the question is how this weak spot can be found in a query protein. Our approach is based on the utilization of the computational tools for the per-residue evaluation of intrinsic disorder predisposition to search for the "weakest spot" of a query protein (i.e., the region(s) with the highest local predisposition for intrinsic disorder). When such "weakest spot" is found, it can be stabilized through a limited number of point mutations by introducing order-promoting residues at hot spots, thereby increasing structural stability of a protein as a whole. Using this approach, we were able to obtain stable mutant forms of several globular proteins, such as Gαo, GFP, ribosome protein L1, and circular permutant of apical domain of GroEL.

Understanding the importance of the aromatic amino-acid residues as hot-spots

2013 ◽  
Vol 1834 (1) ◽  
pp. 404-414 ◽  
Author(s):  
I.S. Moreira ◽  
J.M. Martins ◽  
R.M. Ramos ◽  
P.A. Fernandes ◽  
M.J. Ramos
Keyword(s):  
Amino Acid ◽  
Hot Spots ◽  
Aromatic Amino Acid ◽  
Amino Acid Residues

Conserved features of complexes of TATA-box binding proteins with DNA

2016 ◽  
Vol 14 (02) ◽  
pp. 1641007 ◽  
Author(s):  
Olga Zanegina ◽  
Evgeniy Aksianov ◽  
Andrei V. Alexeevski ◽  
Anna Karyagina ◽  
Sergei Spirin
Keyword(s):  
Comparative Analysis ◽  
Amino Acid ◽  
Hydrogen Bonds ◽  
Protein Interaction ◽  
Binding Proteins ◽  
Tata Box ◽  
Amino Acid Residues ◽  
Protein Interface ◽  
Partial Symmetry ◽  
Dna Protein Interaction

A comparative analysis of all available structures of complexes of TATA-box binding proteins (TBPs) with DNA is performed. Conserved features of DNA–protein interaction are described, including nine amino acid residues that form conserved hydrogen bonds, 13 residues participating in formation of two conserved hydrophobic clusters at DNA–protein interface, and four conserved water-mediated contacts. Partial symmetry of conserved contacts reflects quasi-symmetry of TBP structure.

scholarly journals Prediction of amyloidogenicity based on the n-gram analysis

2016 ◽  
Author(s):  
Michał Jan Burdukiewicz ◽  
Piotr Sobczyk ◽  
Stefan Rödiger ◽  
Anna Duda-Madej ◽  
Paweł Mackiewicz ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Hot Spots ◽  
Permutation Test ◽  
Strongly Correlated ◽  
Amino Acid Residues ◽  
Data Set ◽  
Amyloid Peptides ◽  
External Data ◽  
N Gram

Amyloids are proteins associated with the number of clinical disorders (e.g., Alzheimer's, Creutzfeldt-Jakob's and Huntington's diseases). Despite their diversity, all amyloid proteins can undergo aggregation initiated by 6- to 15-residue segments, called hot spots. To find the patterns defining the hot-spots, we trained predictors of amyloidogenicity, using n-grams and random forest classifiers, based on data collected in the AmyLoad database. Only the most informative n-grams, selected by our Quick Permutation Test, were considered. Since the amyloidogenicity may not depend on the exact sequence of amino acids but on more general properties of amino acids, we tested 524,284 reduced amino acid alphabets of different lengths (three to six letters) to find the alphabet providing the best performance in cross-validation. The predictor based on this alphabet, called AmyloGram, was benchmarked against the most popular tools for the detection of amyloid peptides using an external data set and obtained the highest values of performance measures (AUC: 0.90, MCC: 0.63). Our results showed sequential patterns in the amyloids, which are strongly correlated with hydrophobicity, a tendency to form ß-sheets and rigidity of amino acid residues. Among the most informative n-grams of AmyloGram we identified 15 that were already confirmed experimentally. AmyloGram is available as a web-server: www.smorfland.uni.wroc.pl/amylogram/. The code and results are publicly available at: www.github.com/michbur/prediction_amyloidogenicity_ngram/.

Substrate Recognition by Vitamin K-Dependent Carboxylase

1987 ◽  
Vol 57 (01) ◽  
pp. 017-019 ◽  
Author(s):  
Magda M W Ulrich ◽  
Berry A M Soute ◽  
L Johan M van Haarlem ◽  
Cees Vermeer
Keyword(s):  
Amino Acid ◽  
Vitamin K ◽  
Substrate Recognition ◽  
Bovine Liver ◽  
Amino Acid Residues

SummaryDecarboxylated osteocalcins were prepared and purified from bovine, chicken, human and monkey bones and assayed for their ability to serve as a substrate for vitamin K-dependent carboxylase from bovine liver. Substantial differences were observed, especially between bovine and monkey d-osteocalcin. Since these substrates differ only in their amino acid residues 3 and 4, it seems that these residues play a role in the recognition of a substrate by hepatic carboxylase.

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