scholarly journals Amino-acid site variability among natural and designed proteins

PeerJ ◽  
2013 ◽  
Vol 1 ◽  
pp. e211 ◽  
Author(s):  
Eleisha L. Jackson ◽  
Noah Ollikainen ◽  
Arthur W. Covert ◽  
Tanja Kortemme ◽  
Claus O. Wilke
Keyword(s):  
Amino Acid ◽  
Acid Site ◽  
Amino Acid Site ◽  
Designed Proteins ◽  
Site Variability

scholarly journals Amino-acid site variability among natural and designed proteins

2013 ◽  
Author(s):  
Eleisha L. Jackson ◽  
Noah Ollikainen ◽  
Arthur W. Covert III ◽  
Tanja Kortemme ◽  
Claus O. Wilke
Keyword(s):  
Amino Acid ◽  
Protein Design ◽  
Protein Sequences ◽  
Structural Constraints ◽  
Scoring Functions ◽  
Solvent Exposure ◽  
Backbone Flexibility ◽  
Hydrophobic Residues ◽  
Designed Proteins ◽  
Site Variability

Computational protein design attempts to create protein sequences that fold stably into pre-specified structures. Here we compare alignments of designed proteins to alignments of natural proteins and assess how closely designed sequences recapitulate patterns of sequence variation found in natural protein sequences. We design proteins using RosettaDesign, and we evaluate both fixed-backbone designs and variable-backbone designs with different amounts of backbone flexibility. We find that proteins designed with a fixed backbone tend to underestimate the amount of site variability observed in natural proteins while proteins designed with an intermediate amount of backbone flexibility result in more realistic site variability. Further, the correlation between solvent exposure and site variability in designed proteins is lower than that in natural proteins. This finding suggests that site variability is too uniform across different solvent exposure states (i.e., buried residues are too variable or exposed residues too conserved). When comparing the amino acid frequencies in the designed proteins with those in natural proteins we find that in the designed proteins hydrophobic residues are underrepresented in the core. From these results we conclude that intermediate backbone flexibility during design results in more accurate protein design and that either scoring functions or backbone sampling methods require further improvement to accurately replicate structural constraints on site variability.

α-Amino Acid Derived Benzimidazole-Linked Rhodamines: A Case of Substitution Effect at the Amino Acid Site toward Spiro Ring Opening for Selective Sensing of Al3+ Ions

2017 ◽  
Vol 56 (15) ◽  
pp. 8889-8899 ◽  
Author(s):  
Anupam Majumdar ◽  
Subhendu Mondal ◽  
Constantin G. Daniliuc ◽  
Debashis Sahu ◽  
Bishwajit Ganguly ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Site ◽  
Ring Opening ◽  
Substitution Effect ◽  
Amino Acid Site

Membrane-Bound γ-Glutamyl Transpeptidase. Evidence that it is a Component of the 'Amino Acid Site' of Certain Neutral Amino Acid Transport Systems

1972 ◽  
Vol 50 (5) ◽  
pp. 524-528 ◽  
Author(s):  
Robert P. Bodnaryk
Keyword(s):  
Amino Acid ◽  
Acid Site ◽  
Amino Acid Transport ◽  
Amino Acid Site ◽  
Neutral Amino Acid ◽  
Transport Systems ◽  
Acid Transport ◽  
Membrane Bound ◽  
Glutamyl Transpeptidase ◽  
Transport Site

A membrane-bound γ-glutamyl transpeptidase is likely to be a key component of the 'amino acid site' of certain neutral amino acid transport systems. The hypothesis is in keeping with the Orlowski–Meister concept of a γ-glutamyl cycle for some forms of amino acid transport, and it is supported experimentally by a demonstration that the specificity of a γ-glutamyl transpeptidase (described herein) is virtually the same as the affinity of an amino acid site (described by Hajjar and Curran) for phenylalanine and 16 of its variously substituted analogues.Thus, both transpeptidase and transport site have a greater specificity for phenylalanine analogues having electron-withdrawing groups as substituents in the benzene ring than phenylalanine itself, and reduced specificity for analogues with electron-releasing substituents in the ring. The order of specificity according to ring substitution was −NO2 > −Cl > −F > −H > −CH3 > −OH > −NH2 for both systems. Again, the free α-amino group of phenylalanine plays a key role in the binding of the amino acid to the site, and it is also essential for the transpeptidase. Finally, the essential feature of the carboxyl group for binding of a neutral amino acid by the transport site is the −C = O group and this group is essential for maintaining the γ-glutamyl acceptor properties of an acceptor.

scholarly journals Amino-acid site variability among natural and designed proteins

2013 ◽  
Author(s):  
Eleisha L. Jackson ◽  
Noah Ollikainen ◽  
Arthur W. Covert III ◽  
Tanja Kortemme ◽  
Claus O. Wilke
Keyword(s):  
Amino Acid ◽  
Protein Design ◽  
Protein Sequences ◽  
Structural Constraints ◽  
Scoring Functions ◽  
Solvent Exposure ◽  
Backbone Flexibility ◽  
Hydrophobic Residues ◽  
Designed Proteins ◽  
Site Variability

Computational protein design attempts to create protein sequences that fold stably into pre-specified structures. Here we compare alignments of designed proteins to alignments of natural proteins and assess how closely designed sequences recapitulate patterns of sequence variation found in natural protein sequences. We design proteins using RosettaDesign, and we evaluate both fixed-backbone designs and variable-backbone designs with different amounts of backbone flexibility. We find that proteins designed with a fixed backbone tend to underestimate the amount of site variability observed in natural proteins while proteins designed with an intermediate amount of backbone flexibility result in more realistic site variability. Further, the correlation between solvent exposure and site variability in designed proteins is lower than that in natural proteins. This finding suggests that site variability is too uniform across different solvent exposure states (i.e., buried residues are too variable or exposed residues too conserved). When comparing the amino acid frequencies in the designed proteins with those in natural proteins we find that in the designed proteins hydrophobic residues are underrepresented in the core. From these results we conclude that intermediate backbone flexibility during design results in more accurate protein design and that either scoring functions or backbone sampling methods require further improvement to accurately replicate structural constraints on site variability.

Substrate specificity of ribosomal peptidyl transferase: 2′(3′)-O-aminoacyl nucleosides as acceptors of the peptide chain on the amino acid site

1969 ◽  
Vol 43 (1) ◽  
pp. 13-24 ◽  
Author(s):  
Ivan Rychlík ◽  
Jiřina Černá ◽  
Stanislav Chládek ◽  
Jiří Žemlička ◽  
Zuzana Haladová
Keyword(s):  
Amino Acid ◽  
Substrate Specificity ◽  
Acid Site ◽  
Amino Acid Site ◽  
Peptide Chain ◽  
Peptidyl Transferase

scholarly journals Protein stability: a single recorded mutation aids in predicting the effects of other mutations in the same amino acid site

2011 ◽  
Vol 27 (23) ◽  
pp. 3286-3292 ◽  
Author(s):  
Gilad Wainreb ◽  
Lior Wolf ◽  
Haim Ashkenazy ◽  
Yves Dehouck ◽  
Nir Ben-Tal
Keyword(s):  
Amino Acid ◽  
Protein Stability ◽  
Acid Site ◽  
Amino Acid Site

scholarly journals Evolution of HLA Class II Molecules: Allelic and Amino Acid Site Variability Across Populations

Genetics ◽  
1999 ◽  
Vol 152 (1) ◽  
pp. 393-400 ◽  
Author(s):  
Hugh Salamon ◽  
William Klitz ◽  
Simon Easteal ◽  
Xiaojiang Gao ◽  
Henry A Erlich ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Site ◽  
Balancing Selection ◽  
Amino Acid Level ◽  
Class Ii ◽  
Acid Sites ◽  
Hla Class Ii ◽  
Amino Acid Site ◽  
Significant Difference ◽  
Hla Class Ii Molecules

Abstract Analysis of the highly polymorphic β1 domains of the HLA class II molecules encoded by the DRB1, DQB1, and DPB1 loci reveals contrasting levels of diversity at the allele and amino acid site levels. Statistics of allele frequency distributions, based on Watterson’s homozygosity statistic F, reveal distinct evolutionary patterns for these loci in ethnically diverse samples (26 populations for DQB1 and DRB1 and 14 for DPB1). When examined over all populations, the DQB1 locus allelic variation exhibits striking balanced polymorphism (P < 10-4), DRB1 shows some evidence of balancing selection (P < 0.06), and while there is overall very little evidence for selection of DPB1 allele frequencies, there is a trend in the direction of balancing selection (P < 0.08). In contrast, at the amino acid level all three loci show strong evidence of balancing selection at some sites. Averaged over polymorphic amino acid sites, DQB1 and DPB1 show similar deviation from neutrality expectations, and both exhibit more balanced polymorphic amino acid sites than DRB1. Across ethnic groups, polymorphisms at many codons show evidence for balancing selection, yet data consistent with directional selection were observed at other codons. Both antigen-binding pocket- and non-pocket-forming amino acid sites show overall deviation from neutrality for all three loci. Only in the case of DRB1 was there a significant difference between pocket- and non-pocket-forming amino acid sites. Our findings indicate that balancing selection at the MHC occurs at the level of polymorphic amino acid residues, and that in many cases this selection is consistent across populations.

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