scholarly journals Probing Structural Features of Alzheimer’s Amyloid-β Pores in Bilayers Using Site-Specific Amino Acid Substitutions

Biochemistry ◽  
2012 ◽  
Vol 51 (3) ◽  
pp. 776-785 ◽  
Author(s):  
Ricardo Capone ◽  
Hyunbum Jang ◽  
Samuel A. Kotler ◽  
Bruce L. Kagan ◽  
Ruth Nussinov ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amyloid Β ◽  
Structural Features ◽  
Amino Acid Substitutions ◽  
Site Specific ◽  
Specific Amino Acid

scholarly journals Comparing mutagenesis and simulations as tools for identifying functionally important sequence changes for protein thermal adaptation

2018 ◽  
Vol 116 (2) ◽  
pp. 679-688 ◽  
Author(s):  
Ming-ling Liao ◽  
George N. Somero ◽  
Yun-wei Dong
Keyword(s):  
Amino Acid ◽  
Thermal Adaptation ◽  
Site Directed Mutagenesis ◽  
Dynamics Simulation ◽  
Amino Acid Substitutions ◽  
Thermal Stabilities ◽  
Specific Amino Acid ◽  
Enzyme Thermal Stability ◽  
And Function

Comparative studies of orthologous proteins of species evolved at different temperatures have revealed consistent patterns of temperature-related variation in thermal stabilities of structure and function. However, the precise mechanisms by which interspecific variations in sequence foster these adaptive changes remain largely unknown. Here, we compare orthologs of cytosolic malate dehydrogenase (cMDH) from marine molluscs adapted to temperatures ranging from −1.9 °C (Antarctica) to ∼55 °C (South China coast) and show how amino acid usage in different regions of the enzyme (surface, intermediate depth, and protein core) varies with adaptation temperature. This eukaryotic enzyme follows some but not all of the rules established in comparisons of archaeal and bacterial proteins. To link the effects of specific amino acid substitutions with adaptive variations in enzyme thermal stability, we combined site-directed mutagenesis (SDM) and in vitro protein experimentation with in silico mutagenesis using molecular dynamics simulation (MDS) techniques. SDM and MDS methods generally but not invariably yielded common effects on protein stability. MDS analysis is shown to provide insights into how specific amino acid substitutions affect the conformational flexibilities of mobile regions (MRs) of the enzyme that are essential for binding and catalysis. Whereas these substitutions invariably lie outside of the MRs, they effectively transmit their flexibility-modulating effects to the MRs through linked interactions among surface residues. This discovery illustrates that regions of the protein surface lying outside of the site of catalysis can help establish an enzyme’s thermal responses and foster evolutionary adaptation of function.

scholarly journals Site-specific amino acid alterations in Ca2+ binding domains in calmodulin impair activation of RBC Ca(2+)-ATPase

1992 ◽  
Vol 62 (1) ◽  
pp. 77-78 ◽  
Author(s):  
D. Kosk-Kosicka ◽  
T. Bzdega ◽  
A. Wawrzynow ◽  
D.M. Watterson ◽  
T.J. Lukas
Keyword(s):  
Amino Acid ◽  
Site Specific ◽  
Specific Amino Acid ◽  
Binding Domains

scholarly journals Contribution of Specific Amino Acid Changes in Penicillin Binding Protein 1 to Amoxicillin Resistance in ClinicalHelicobacter pyloriisolates

2010 ◽  
Vol 55 (1) ◽  
pp. 101-109 ◽  
Author(s):  
Nadia N. Qureshi ◽  
Dimitrios Morikis ◽  
Neal L. Schiller
Keyword(s):  
Amino Acid ◽  
Homology Modeling ◽  
Binding Protein ◽  
Site Directed Mutagenesis ◽  
Amino Acid Substitutions ◽  
Peptic Ulcers ◽  
Penicillin Binding Protein ◽  
Specific Amino Acid ◽  
Binding Cleft ◽  
H Pylori

ABSTRACTAmoxicillin is commonly used to treatHelicobacter pylori, a major cause of peptic ulcers, stomach cancer, and B-cell mucosa-associated lymphoid tissue lymphoma. Amoxicillin resistance inH. pyloriis increasing steadily, especially in developing countries, leading to treatment failures. In this study, we characterize the mechanism of amoxicillin resistance in the U.S. clinical isolate B258. Transformation of amoxicillin-susceptible strain 26695 with the penicillin binding protein 1 gene (pbp1) from B258 increased the amoxicillin resistance of 26695 to equal that of B258, while studies using biotinylated amoxicillin showed a decrease in the binding of amoxicillin to the PBP1 of B258. Transformation with 4pbp1fragments, each encompassing several amino acid substitutions, combined with site-directed mutagenesis studies, identified 3 amino acid substitutions in PBP1 of B258 which affected amoxicillin susceptibility (Val 469 Met, Phe 473 Leu, and Ser 543 Arg). Homology modeling showed the spatial orientation of these specific amino acid changes in PBP1 from 26695 and B258. The results of these studies demonstrate that amoxicillin resistance in the clinical U.S. isolate B258 is due solely to an altered PBP1 protein with a lower binding affinity for amoxicillin. Homology modeling analyses using previously identified amino acid substitutions of amoxicillin-resistant PBP1s demonstrate the importance of specific amino acid substitutions in PBP1 that affect the binding of amoxicillin in the putative binding cleft, defining those substitutions deemed most important in amoxicillin resistance.

scholarly journals Specific KRAS amino acid substitutions and EGFR mutations predict site-specific recurrence and metastasis following non-small-cell lung cancer surgery

2016 ◽  
Vol 115 (3) ◽  
pp. 346-353 ◽  
Author(s):  
Stéphane Renaud ◽  
Joseph Seitlinger ◽  
Pierre-Emmanuel Falcoz ◽  
Mickaël Schaeffer ◽  
Anne-Claire Voegeli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Amino Acid ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Lung Cancer Surgery ◽  
Small Cell ◽  
Egfr Mutations ◽  
Amino Acid Substitutions ◽  
Small Cell Lung ◽  
Site Specific

scholarly journals Prediction of Site-Specific Amino Acid Distributions and Limits of Divergent Evolutionary Changes in Protein Sequences

2004 ◽  
Vol 22 (3) ◽  
pp. 630-638 ◽  
Author(s):  
Markus Porto ◽  
H. Eduardo Roman ◽  
Michele Vendruscolo ◽  
Ugo Bastolla
Keyword(s):  
Amino Acid ◽  
Protein Sequences ◽  
Site Specific ◽  
Specific Amino Acid ◽  
Evolutionary Changes
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