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J L Risler

Publications and source records attributed to J L Risler.

36 records · Page 2Linked to original sources
PubMed1993

Dot-plot comparisons by multivariate analysis (DOCMA): a tool for classifying protein sequences.

A method aimed at classifying protein sequences without resorting to pairwise alignment is presented. Called DOCMA (DOt-plot Comparisons by Multivariate Analysis), it is based on a multivariate analysis of the pairwise dot-plots between all the sequences in the set. The dot-plots are first simplified by considering only the projections of the 'diagonal' segments of similarity onto the axes. From these projections a data matrix is built, in which each column is representative of the comparisons of one given sequence with all the other ones. This data matrix is then transformed into a distance matrix by a chi-squared analysis, from which the coordinates of the sequences in an orthonormal Euclidean space are obtained. The sequences are finally classified by a dynamic clustering procedure followed by a search for strong clusters. Application of this method to protein families such as the globins, the cytochromes c and the aminoacyl-tRNA synthetases shows that it is quite effective in delineating subgroups that contain even distantly related sequences.

Algorithms↗
PubMed1992

A comparison of several similarity indices used in the classification of protein sequences: a multivariate analysis.

The present work describes an attempt to identify reliable criteria which could be used as distance indices between protein sequences. Seven different criteria have been tested: i and ii) the scores of the alignments as given by the BESTFIT and the FASTA programs; iii) the ratio parameter, i.e. the BESTFIT score divided by the length of the aligned peptides; iv and v) the statistical significance (Z-scores) of the scores calculated by BESTFIT and FASTA, as obtained by comparison with shuffled sequences; vi) the Z-scores provided by the program RELATE which performs a segment-by-segment comparison of 2 sequences, and vii) an original distance index calculated by the program DOCMA from all the pairwise dotplots between the sequences. These 7 criteria have been tested against the aminoacid sequences of 39 globins and those of the 20 aminoacyl-tRNA synthetases from E. coli. The distances between the sequences were analyzed by the multivariate analysis techniques. The results show that the distances calculated from the scores of the pairwise alignments are not adequately sensitive. The Z-score from RELATE is not selective enough and too demanding in computer time. Three criteria gave a classification consistent with the known similarities between the sequences in the sets, namely the Z-scores from BESTFIT and FASTA and the multiple dotplot comparison distance index from DOCMA.

Algorithms↗
PubMed1992

Evolutionary divergence plots of homologous proteins.

A simple and efficient method is described for analyzing quantitatively multiple protein sequence alignments and finding the most conserved blocks as well as the maxima of divergence within the set of aligned sequences. It consists of calculating the mean distance and the root-mean-square distance in each column of the multiple alignment, averaging the values in a window of defined length and plotting the results as a function of the position of the window. Due attention is paid to the presence of gaps in the columns. Several examples are provided, using the sequences of several cytochromes c, serine proteases, lysozymes and globins. Two distance matrices are compared, namely the matrix derived by Gribskov and Burgess from the Dayhoff matrix, and the Risler Structural Superposition Matrix. In each case, the divergence plots effectively point to the specific residues which are known to be essential for the catalytic activity of the proteins. In addition, the regions of maximum divergence are clearly delineated. Interestingly, they are generally observed in positions immediately flanking the most conserved blocks. The method should therefore be useful for delineating the peptide segments which will be good candidates for site-directed mutagenesis and for visualizing the evolutionary constraints along homologous polypeptide chains.

Amino Acid Sequence↗
PubMed1991

Structural similarities in glutaminyl- and methionyl-tRNA synthetases suggest a common overall orientation of tRNA binding.

Detailed comparisons between the structures of the tRNA-bound Escherichia coli glutaminyl-tRNA (Gln-tRNA) synthetase [L-glutamine:tRNA(Gln) ligase (AMP-forming), EC 6.1.1.18] and recently refined E. coli methionyl-tRNA (Met-tRNA) synthetase [L-methionine:tRNA(Met) ligase (AMP-forming), EC 6.1.1.10] reveal significant similarities beyond the anticipated correspondence of their respective dinucleotide-fold domains. One similarity comprises a 23-amino acid alpha-helix-turn-beta-strand motif found in each enzyme within a domain that is inserted between the two halves of the dinucleotide binding fold. A second correspondence, which consists of two alpha-helices connected by a large loop and beta-strand, is located in the Gln-tRNA synthetase within a region that binds the inside corner of the "L"-shaped tRNA molecule. This structural motif contains a long alpha-helix, which extends along the entire length of the D and anticodon stems of the complexed tRNA. We suggest that the positioning of this helix relative to the dinucleotide fold plays a critical role in ensuring the proper global orientation of tRNA(Gln) on the surface of the enzyme. The structural correspondences suggest a similar overall orientation of binding of tRNA(Met) and tRNA(Gln) to their respective synthetases.

Amino Acyl-tRNA Synthetases↗
PubMed1990

Crystallographic study at 2.5 A resolution of the interaction of methionyl-tRNA synthetase from Escherichia coli with ATP.

The crystal structure of the tryptic fragment of the methionyl-tRNA synthetase from Escherichia coli, complexed with ATP, has been refined to a crystallographic R-factor of 0.220, at 2.5 A resolution (for 4433 protein atoms). In the last stages of the refinement, the simulated annealing refinement method was fully applied, contributing to a drastic improvement of the model and the identification of the missing atoms. In the final model, the root-mean-square deviation from ideality for bond distances is 0.021 A and for angle distances is 0.054 A. The position of the zinc ion has been confirmed and is located near the active site. The tryptic fragment is composed of two globular domains. The first domain, from the N terminus to Thr360, contains a nucleotide-binding fold into which two long polypeptides of 101 and 70 residues are inserted. The nucleotide-binding fold is strengthened by the presence of the zinc ion in the vicinity of the active site. The second domain, up to Pro526, is mainly alpha-helical. The C-terminal polypeptide, Phe527 to Lys551, folds back towards the first domain, making a link between the two domains. The heptapeptide 528-534 partly shapes a deep cavity that plunges into the central core of the nucleotide-binding fold, where the ATP molecule is located. The adenine ring, deeply buried in the bottom of the cleft, is blocked between the first helix HA, and the strands A and D of the beta-sheet and makes no polar interaction with the enzyme. The 2' and 3' hydroxyl groups of the ribose, whose conformation is C2' endo, interact with the main-chain carbonyl oxygen atoms of Ile231 and Glu241, respectively. The side-chain nitrogen atom of Lys142 is at hydrogen-bonding distance from the ring oxygen O-4' of the ribose. One of the alpha-phosphate oxygen atoms and one of the gamma-phosphate oxygen atoms interact with the imidazole ring of His21, which is well conserved in many of the known synthetases; this indicates a possible crucial role for this residue in binding ATP. The beta-phosphate group is linked to the main-chain carbonyl oxygen atom of Tyr15 through an intermediate water molecule. The gamma-phosphate group interacts with the carbonyl oxygen atom and the side-chain of Asn17.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1988

Amino acid substitutions in structurally related proteins. A pattern recognition approach. Determination of a new and efficient scoring matrix.

Amino acid substitutions in evolutionarily related proteins have been studied from a structural point of view. We consider here that an amino acid al in a protein p1 has been replaced by the amino acid a2 in the structurally similar protein p2 if, after superposition of the p1 and p2 structures, the a1 and a2 C alpha atoms are no more than 1.2 A apart. Thirty-two proteins, grouped in 11 classes, have been analysed by this method. This produced 2860 amino acid pairs (substitutions), which were analysed by multi-dimensional statistical methods. The main results are as follows: (1) according to the observed exchangeability of amino acid side-chains, only four groups (strong clusters) could be delineated; (i) Ile and Val, (ii) Leu and Met, (iii) Lys, Arg and Gln, and (iv) Tyr and Phe. The other residues could not be classified. (2) The matrix of distances between amino acids, or scoring matrix, determined from this study, is different from any other published matrix. (3) Except for the distance matrices based on the chemical properties of amino acid side-chains, which can be grouped together, all other published matrices are different from one another. (4) The distance matrix determined in this study seems to be very efficient for aligning distantly related protein sequences.

Amino Acid Sequence↗
PubMed1985

Crystal structure study of Opsanus tau parvalbumin by multiwavelength anomalous diffraction.

The crystal structure of a small calcium-binding protein, the parvalbumin IIIf from Opsanus tau in which Tb was substituted for Ca, has been analysed by multiwavelength anomalous diffraction. Data at a resolution of 2.3 A were collected at three wavelengths near the L3 absorption edge of Tb (1.645-1.650 A), using the synchrotron radiation emitted by a storage ring and a multiwire proportional counter. The phases of the reflections were determined from this single derivative, without native data. Prior to any refinement, the resulting electron density map shows a good agreement with the model of the homologous carp parvalbumin in regions of identical amino-acid sequence.

Animals↗
PubMed1983

Structural homology in the amino-terminal domains of two aminoacyl-tRNA synthetases.

The three-dimensional structures of two animoacyl-tRNA synthetases, the methionyl-tRNA synthetase from Escherichia coli (MetRS) and the tyrosyl-tRNA synthetase from Bacillus stearothermophilus (TyrRS), show a remarkable similarity over a span of about 140 amino acids. The region of homologous folding corresponds to a five-stranded parallel beta-sheet, including a mononucleotide-binding fold. One cysteine and two histidine residues that were found to be invariant in the amino acid sequences occupy similar places in the nucleotide-binding fold. In TyrRS, these residues are close to the adenylate binding site, and in MetRS to the Mg2+-ATP binding site.

Amino Acid Sequence↗