2gnx Discussion

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Structural Analysis

The structural analysis of the 2GNX protein did not produce any significant matches upon submission to the Dali database. Therefore, a separate analysis of the N-terminal domain and C-terminal domain of the protein was carried out. Results from these analyses showed us that there were no significant matches to the N-terminal domain of the protein. Much research and analysis into the closest search results generated by the Dali database was carried out using various resources. However, none of these resources was able to identify these results as structural matches. It was then concluded that much more thorough research and analysis is required in order to identify the structure of the N-terminal domain of the protein.

An analysis of the C-terminal domain of the protein using the Dali database was able to provide us with some significant structural matches, of high interest being the GAF signalling protein. A CE analysis confirmed that the structure of the GAF protein did indeed match closely to the C-terminal domain of the 2GNX protein. It identified that the GAF protein contained a cGMP ligand binding pocket (Martinez et al, 2002). Using the computational biology software PyMol it was identified that while the 2GNX protein did not contain an exact match of the ligand binding pocket, there were a few residues that did match. Therefore it is likely that the protein does bind with a cGMP ligand. However, since 30 (check number) residues that may comprise the ligand binding pocket of the protein were not found in its PDB file, further research and analysis has to be carried out to confirm that the protein does indeed contain a cGMP ligand-binding pocket.

Functional Analysis

Despite most of the conventional tools failing to return significant results, multiple resources suggest that this protein is related or a part of the olfactory transduction pathway. The results from the symatlas were the first hint of this possibility. Following this, the cis-RED motif results showed that this hypothesis was quite significant.

cis-RED is a database which holds conserved sequence motifs. Motifs, sometimes referred to as modules, are conserved cis-regulatory regions which contain the spatially clustered binding sites of transcription factors. The cis-RED analysis presented 14 modules present in the BC048403 protein. All of these modules are also found in olfactory receptors co-occurring in groups from one to nine. Up to 120 olfactory receptors corresponded to these 14 modules and the most significant results - those with 3 or more co-occurring modules, appear in Table 6 of the results. The two most significant olfactory receptors had 9 modules in common with the BC048403 protein. The top five co-occuring modules were investigated in terms of conservation and expression, however no further results were gained.

Further evidence of this proteins involvement in olfactory transduction is the Micro-Array profiles shown in Figure 6 of the results. These expression profiles were found by searching the neighbouring profiles of the human ortholog FLJ32549. We were hopeful of finding a corresponding olfactory receptor to those found through the cis-RED analysis, however this did not occur.

File:Olf trans path.GIF