A new algorithm for analysis of the homology in protein primary structure

Leluk, Jacek

doi:10.1016/s0097-8485(97)00035-1

Cited by 15 publications

(20 citation statements)

References 24 publications

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“…The multiple alignment of the selected sequences was achieved with the aid of ClustalX [18]–[19] and verified with the algorithm of genetic semihomology [20]–[23]. As for the virus proteins, the sequences show very high conservativity (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…For the preliminary multiple sequence alignment ClustalX [18]–[19] was used, then the alignment was verified and corrected if necessary by manual analysis following the algorithm of genetic semihomology [20]–[23]. The verification concerned the possible genetic relationship between compared positions which were non-identical (possible replacements by single transition/transversion).…”

Section: Methodsmentioning

confidence: 99%

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Study on Phylogenetic Relationships, Variability, and Correlated Mutations in M2 Proteins of Influenza Virus A

Leluk

2011

PLoS ONE

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M2 channel, an influenza virus transmembrane protein, serves as an important target for antiviral drug design. There are still discordances concerning the role of some residues involved in proton transfer as well as the mechanism of inhibition by commercial drugs. The viral M2 proteins show high conservativity; about 3/4 of the positions are occupied by one residue in over 95%. Nine M2 proteins from the H3N2 strain and possibly two proteins from H2N2 strains make a phylogenic cluster closely related to 2RLF. The variability range is limited to 4 residues/position with one exception. The 2RLF protein stands out by the presence of 2 serines at the positions 19 and 50, which are in most other M2 proteins occupied by cysteines. The study of correlated mutations shows that there are several positions with significant mutational correlation that have not been described so far as functionally important. That there are 5 more residues potentially involved in the M2 mechanism of action. The original software used in this work (Consensus Constructor, SSSSg, Corm, Talana) is freely accessible as stand-alone offline applications upon request to the authors. The other software used in this work is freely available online for noncommercial purposes at public services on bioinformatics such as ExPASy or NCBI. The study on mutational variability, evolutionary relationship, and correlated mutation presented in this paper is a potential way to explain more completely the role of significant factors in proton channel action and to clarify the inhibition mechanism by specific drugs.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Study on Phylogenetic Relationships, Variability, and Correlated Mutations in M2 Proteins of Influenza Virus A

Leluk

2011

PLoS ONE

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“…From a maximum 250 homologies, qualified sequences which could represent the PTP1B homologs in different vertebrates were the materials for multiple sequence alignment (MSA) using Clustal Omega (Sievers et al 2011) with input ordered and Phylip output format (http://www.ebi.ac.uk/Tools/msa/clustalo/). The result of MSA was also compared and verified by T-Coffee method (Notredame et al 2000) and the algorithm of genetic semihomology (Leluk 1998; Leluk et al 2001) respectively. The consensus sequence of aligned PTP-non receptor type 1 sequences was then constructed with the aid of Consensus constructor (Fogtman and Lesyng 2005).…”

Section: Methodsmentioning

confidence: 99%

Suggestion of suitable animal models for in vivo studies of protein tyrosine phosphatase 1b (PTP1B) inhibitors using computational approaches

Nguyen

2014

SpringerPlus

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PTP1B is a prototypic enzyme of the superfamily protein tyrosine phosphatases (PTPs) which are critical regulators of tyrosine phosphorylation-dependent signaling events. It is a highly plausible candidate for designing therapeutic inhibitors of obesity and type 2 diabetes (T2D). In this study, a detailed comparative analysis to reveal the evolutionary relationship of human PTP1B among related vertebrates has been addressed.The phylogenetic trees were constructed with maximum likelihood algorithm by PhyML package on the basis of multiple sequence alignment (MSA) by ClustalΩ and T-coffee. Mutational variability of the sequences corresponding to the 3D structure (pdb: 2vev) was analyzed with Consurf software. The comparative analysis by inhibitor docking to different models was made to confirm the suitability of models.As a result, the PTP1B or PTP non-receptor type 1 homologies show high conservativity where about 70% positions on primary structures are conserved. Within PTP domain (3–277), the most variable positions are 12, 13, 19 and 24 which is a part of the second aryl binding site. Moreover, there are important evolutional mutations that can change the conformation of the proteins, for instance, hydrophilic N139 changed to hydrophobic Gly (mPTP1B); E132 to proline in the hydrophobic core structure or Y46 to cystein in pTyr recognition loop. These variations/differences should be taken into account for rational inhibitor design and in choosing suitable animal models for drug testing and evaluation. Moreover, our study suggests critically potential models which are Heterocephalus glaber, Tupaia chinensis, Sus scrofa, and Rattus norvegicus in addition to the best one Macaca fascicularis. Among these models, the H.glaber and R.norvegicus are preferable over M.musculus thanks to their similarity in binding affinity and binding modes to investigated PTP1B inhibitors.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-3-380) contains supplementary material, which is available to authorized users.

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“…The amino‐acid sequence of AMCI was compared with other proteins stored in the Protein Sequence Swiss‐Prot database, and the degree of homology was established using the semihom program [19].…”

Section: Methodsmentioning

confidence: 99%

Primary structure and properties of the cathepsin G/chymotrypsin inhibitor from the larval hemolymph of Apis mellifera

Bania

Stachowiak

Polanowski

1999

European Journal of Biochemistry

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A member of the Ascaris inhibitor family exhibiting anti-cathepsin G and anti-chymotrypsin activity was purified from the larval hemolymph of the honey bee (Apis mellifera). Three forms of the inhibitor, designated AMCI 1±3, were isolated using gel filtration and anion-exchange chromatographies followed by reverse-phase HPLC. The amino-acid analyses indicated that AMCI-1 and AMCI-2 have an identical composition whereas AMCI-3 is shorter by two residues (Thr, Arg). All three forms contain as many as 10 cysteine residues and lack tryptophan, tyrosine, and histidine. The sequence of the isoinhibitors showed that the major form (AMCI-1) consisting of 56 amino-acid residues was a single-chain protein of molecular mass 5972 Da, whereas the other two forms were two-chain proteins with a very high residue identity. The AMCI-2 appeared to be derived from AMCI-1, as a result of the Lys24-Thr25 peptide bond splitting, while AMCI-3 was truncated at its N-terminus by the dipeptide Thr25-Arg26. The association constants for the binding of bovine a-chymotrypsin to all purified forms of the inhibitor were high and nearly identical, ranging from 4.8 Â 10 10 m 21 for AMCI-1 to 2.7 Â 10 9 m 21 for AMCI-3. The sensitivity of cathepsin G to inhibition by each inhibitor was different. Only the association constant for the interaction of this enzyme with AMCI-1 was high (2 Â 10 8 m 21) whereas those for AMCI-2 and AMCI-3 were significantly lower, and appeared to be 3.7 Â 10 7 m 21 and 4.5 Â 10 6 m 21 , respectively. The reactive site of the inhibitor, as identified by cathepsin G degradation and chemical modification, was found to be at Met30-Gln31. A search in the Protein Sequence Swiss-Prot databank revealed a significant degree of identity (44%) between the primary structure of AMCI and the trypsin isoinhibitor from Ascaris sp (ATI) .On the basis of the cysteine residues alignment, the position of the reactive site as well as some sequence homology, the cathepsin G/chymotrypsin inhibitor from larval hemolymph of the honey bee may be considered to be a member of the Ascaris inhibitor family.

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A new algorithm for analysis of the homology in protein primary structure

Cited by 15 publications

References 24 publications

Study on Phylogenetic Relationships, Variability, and Correlated Mutations in M2 Proteins of Influenza Virus A

Study on Phylogenetic Relationships, Variability, and Correlated Mutations in M2 Proteins of Influenza Virus A

Suggestion of suitable animal models for in vivo studies of protein tyrosine phosphatase 1b (PTP1B) inhibitors using computational approaches

Primary structure and properties of the cathepsin G/chymotrypsin inhibitor from the larval hemolymph of Apis mellifera

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