Propensity of Amino Acids in Loop Regions Connecting Beta-Strands

Minuchehr, Zarrin; Goliaei, Bahram

doi:10.2174/0929866053765617

Cited by 6 publications

(7 citation statements)

References 21 publications

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“…A value > 1.0 means that the pair has an occurrence in the chameleon sequences which is higher than its incident in the PDB, suggesting that the pair has a preference for adopting chameleon sequences. Furthermore, Ʃx (a ± 1) values lower than unity suggest less preference for the pair in the chameleon sequences, all of our singlet and doublet propensity calculations were mentioned in our previous studies [25,29].…”

Section: Residue Occurrencesupporting

confidence: 67%

Chameleon sequences in neurodegenerative diseases

Bahramali

Goliaei

Minuchehr

et al. 2016

Biochemical and Biophysical Research Communications

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Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to "helix to strand (HE)", "helix to coil (HC)" and "strand to coil (CE)" alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases.

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Section: Residue Occurrencesupporting

confidence: 67%

Chameleon sequences in neurodegenerative diseases

Bahramali

Goliaei

Minuchehr

et al. 2016

Biochemical and Biophysical Research Communications

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“…The Rbfox β 2 β 3 loop is acidic. Therefore, we mutated E152 on the tip of β 2 β 3 loop to Thr, one of the favorable amino acids observed in loops connecting β-sheets 25 ( Fig. 1b,c ).…”

Section: Resultsmentioning

confidence: 99%

Targeted inhibition of oncogenic miR-21 maturation with designed RNA-binding proteins

et al. 2016

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The RNA Recognition Motif (RRM) is the largest family of eukaryotic RNA-binding proteins. Engineered RRMs with new specificity would provide valuable tools and an exacting test of our understanding of specificity. We have achieved the first successful re-design of the specificity of an RRM using rational methods and demonstrated re-targeting of activity in cells. We engineered the conserved RRM of human Rbfox proteins to specifically bind to the terminal loop of miR-21 precursor with high affinity and inhibit its processing by Drosha and Dicer. We further engineered Giardia Dicer by replacing its PAZ domain with the designed RRM. The reprogrammed enzyme degrades pre-miR-21 specifically in vitro and suppresses mature miR-21 levels in cells, which results in increased expression of PDCD4 and significantly decreased viability for cancer cells. The results demonstrate the feasibility of engineering the sequence-specificity of RRMs and of using this ubiquitous platform for diverse biological applications.

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“…Based on Anfinsen's dogma, at least for small globular proteins, the native structure is determined by the protein's amino acid sequence alone. 30 This sequence-structure relationship was investigated for fragments of two consecutive amino acids (or doublets), [31][32][33] triplets, 34 and even longer sequences, 11,17 which in the latter case are commonly considered as structural alphabets for proteins. Nevertheless, all previous studies focused on the effects of sequence specificity on the backbone rather than on side chains.…”

Section: Introductionmentioning

confidence: 99%

SDRL: a sequence-dependent protein side-chain rotamer library

2015

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Since the introduction of the first protein side-chain rotamer library (RL) almost half a century ago, RLs have been components of many programs and algorithms in structural bioinformatics. Based on the dependence of side-chain dihedral angles on the local backbone, three types of RLs have been identified: backbone-independent, secondary-structure-dependent and backbone-dependent. In all previous studies, the effect of sequence specificity on side-chain conformational preferences was neglected. In the effort to develop a new class of RLs, we considered that the side-chain conformation of the central residue in each triplet on a protein backbone depends on the sequence of the triplet; therefore, we developed a sequence-dependent rotamer library (SDRL). To accomplish this, 400 possible triplet sequences for 18 natural amino acids as the central residue, which corresponds to 7200 triplet sequences in total, were considered. Searching the set of 11 546 selected PDB entries for the 7200 triplet sequences resulted in 2 364 541 instances occurring for 18 amino acids. Our results show that Leu and Val experience minimal impact from the adjacent residues in adopting side-chain conformations. Cys, Ile, Trp, His, Asp, Met, Glu, Gln, Arg and Lys, on the other hand, adopt their side-chain conformations mostly based on the adjacent residues on the backbone. The remaining residue types were moderately dependent on the adjacent residues. Using the new library, side-chain repacking algorithms can find preferred conformations of each residue more easily than with other backbone-independent RLs.

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Propensity of Amino Acids in Loop Regions Connecting Beta-Strands

Cited by 6 publications

References 21 publications

Chameleon sequences in neurodegenerative diseases

Chameleon sequences in neurodegenerative diseases

Targeted inhibition of oncogenic miR-21 maturation with designed RNA-binding proteins

SDRL: a sequence-dependent protein side-chain rotamer library

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