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Biomedical subjects

M L Chiusano

Publications and source records attributed to M L Chiusano.

5 recordsLinked to original sources

Homology modelling of the human eukaryotic initiation factor 5A (eIF-5A).

Homology modelling of the human eIF-5A protein has been performed by using a multiple predictions strategy. As the sequence identity between the target and the template proteins is nearly 30%, which is lower than the commonly used threshold to apply with confidence the homology modelling method, we developed a specific predictive scheme by combining different sequence analyses and predictions, as well as model validation by comparison to structural experimental information. The target sequence has been used to find homologues within sequence databases and a multiple alignment has been created. Secondary structure for each single protein has been predicted and compared on the basis of the multiple sequence alignment, in order to evaluate and adjust carefully any gap. Therefore, comparative modelling has been applied to create the model of the protein on the basis of the optimized sequence alignment. The quality of the model has been checked by computational methods and the structural features have been compared to experimental information, giving us a good validation of the reliability of the model and its correspondence to the protein structure in solution. Last, the model was deposited in the Protein Data Bank to be accessible for studies on the structure-function relationships of the human eIF-5A.

Amino Acid Sequence↗

Second codon positions of genes and the secondary structures of proteins. Relationships and implications for the origin of the genetic code.

The nucleotide frequencies in the second codon positions of genes are remarkably different for the coding regions that correspond to different secondary structures in the encoded proteins, namely, helix, beta-strand and aperiodic structures. Indeed, hydrophobic and hydrophilic amino acids are encoded by codons having U or A, respectively, in their second position. Moreover, the beta-strand structure is strongly hydrophobic, while aperiodic structures contain more hydrophilic amino acids. The relationship between nucleotide frequencies and protein secondary structures is associated not only with the physico-chemical properties of these structures but also with the organisation of the genetic code. In fact, this organisation seems to have evolved so as to preserve the secondary structures of proteins by preventing deleterious amino acid substitutions that could modify the physico-chemical properties required for an optimal structure.

Chemical Phenomena↗

Correlations of nucleotide substitution rates and base composition of mammalian coding sequences with protein structure.

We investigated the relationships between the nucleotide substitution rates and the predicted secondary structures in the three states representation (alpha-helix, beta-sheet, and coil). The analysis was carried out on 34 alignments, each of which comprised sequences belonging to at least four different mammalian orders. The rates of synonymous substitution were found to be significantly different in regions predicted to be alpha-helix, beta-sheet, or coil. Likewise, the nonsynonymous rates also differ, although expectedly at a lower extent, in the three types of secondary structure, suggesting that different selective constraints associated with the different structures are affecting in a similar way the synonymous and nonsynonymous rates. Moreover, the base composition of the third codon positions is different in coding sequence regions corresponding to different secondary structures of proteins.

Animals↗

Organization and nucleotide sequence of the cluster of five histone genes in the polichaete worm Chaetopterus variopedatus: first record of a H1 histone gene in the phylum Annelida.

Histone genes were identified and their nucleotide sequences were determined in the polychaete marine worm Chaetopterus variopedatus. The genes are organized in about 390 clusters of 7.3 kbp. Each cluster contains one copy of the five histone genes. The H1 histone gene present in the clusters is the first ever isolated in the phylum Annelida. The cluster has the unique peculiarity that all genes contain both the replication-dependent and the replication-independent 3' mRNA termination signals. Despite the differences in cluster organization and transcription polarity of the individual histone genes between C. variopedatus and Platynereis dumerilii, the other annelid in which histone genes have been studied, phylogenetic analysis of the encoded amino acid sequences clearly groups together those two organisms in a tree in which the other studied worms find closely related positions on the same evolutionary branch.

Amino Acid Sequence↗

STRIRED: graphical analysis of string repeats.

UNLABELLED: STRIRED is a toolkit to generate a graphical picture of the distribution of 4- to 6-mer repeats in a set of user-defined nucleic acid sequences. AVAILABILITY: The STRIRED package can be downloaded as self-extracting archive (strired.exe) by anonymous FTP from biol.dgbm.unina.it (143.225.252.1), in the directory /software/win95/STRIRED. CONTACT: calogero@biol.dgbm.unina. it.

Base Sequence↗