Sequence homology studies

Research and development efforts in the pharmaceutical and biotech industries depend critically on patent protection for commercially valuable biological molecules. In this context, patent laws broadly require clear disclosure of molecular function. Deriving this essential functional information is far from trivial [101]. Basic sequence homology studies are already a first step in these critical research efforts. Pattern-based approaches focusing on fundamental structural and functional motifs can valuably focus expensive and lengthy laboratory efforts. The power of these approaches will invariably increase with expansion and improvement of data repositories and associated analysis tools. The U.S. Patent and Trademark Office already welcomes these sorts of in silico studies as valuable adjunct evidence in support of a molecule s functional specification. 

In the 2S albumin fi-om B, excelsa, aU of the 8 cysteine residues are involved in the formation of disulfide bridges. Sequence homology studies showed that Ricinus comunis and Helianthus annuus albumin have the highest identity score within a super-fiimily of seed storage proteins (75). 

Detailed sequence homology studies of the two enzymes, MeHNL (EC 4.1.2.37) and HbHNL (EC 4.1.2.39), reveled that HbHNL from H. brasiliensis is highly homologous to the HNL from M. esculenta [27]. Therefore it could be expected that these enzymes resemble each other in substrate specificity as confirmed later by experimental investigations. 

This structural similarity is also reflected in the amino acid sequences of the domains, which show 40% identity. They are thus clearly homologous to each other. The motif structures within the domains superpose equally well but their sequence homology is less, being around 30% between motifs 1 and 2 and 20 Xi between 3 and 4. This study, however, clearly shows that the topological description in terms of four Greek key motifs is also valid at the structural and amino acid sequence levels. 

Crystallographic studies imply that although little sequence homology exists between the different protease cleavage sites, what is conserved is the shape that they adopt within the active site of the enzyme (Prabu-Jeyabalan et al. 2002). This shape has been termed the substrate envelope and represents the consensus volume overlapping the majority of the substrates. Most likely, HIV-1 protease recognizes a particular peptide sequence as being a substrate by a combination of accessibility and the shape the sequence can adopt. 

Cortistatin was discovered as a result of the effort to characterize cortex-specific gene expression modulated by synaptic activity. It was named after its cortical expression and sequence homology to somatostatin (de Lecea et a ., 1996). The characterization of this peptide is yet another example of the use of reverse genetics to study the molecular components of the sleep machinery. 

The gene encoding PBAN was first characterized from H. zea and B. mori [134,137,138,195]. The cDNA was found to encode the 33 amino acid PBAN plus four additional peptides with a common C-terminal FXPRL sequence motif, including that of the diapause hormone of B. mori (Fig. 6). Three additional peptides with the common C-termini and sequence homology to those of H. zea and B. mori have been deduced from cDNA isolated from pheromone glands of several other moths [194,196-200]. Studies conducted to find the post-translational processed peptides indicated that PBAN was found to a greater extent in the mandibular and maxillary clusters than in the labial cluster of neurons... 

In addition to bcl-2, another hitherto completely unexpected target for the actions of chronic lithium and VPA has been identified from the mRNA RT-PCR DD study described above. Another clone, also derived from a transcript whose levels were increased by both lithium and VPA, shows very strong homology to a human mRNA-binding protein, the AUH protein ([54, 55] Genbank accession number X79888). BESTFIT analysis revealed 83.2% sequence homology between this rodent clone and the human AUH protein [54—56]. 

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