Macromolecular Structure Databases - Essays in Bioinformatics - page 145

highlighted: 117-119, 230, 268, 270, and 279. Glancing at the 3D Domain display in the
Structure Summary page, we note that all of these residues lie in domain 3. We now
focus our attention on this domain.
Viewing Structure Neighbors of a 3D Domain. Given that this enzyme is a dimer,
we arbitrarily choose domain 3 from chain A, the accession of which is thus 1B8GA3. By
clicking on the 3D Domain bar at a point within domain 3, we are taken to the VAST
Structure Neighbors page for this domain, where we find nearly 200 structure neighbors.
Restricting the Search by Taxonomy. Perhaps we would now like to identify some
of the most evolutionarily distant structure neighbors of domain 1B8GA3 as a means of
finding conserved residues that may be associated with its binding and/or catalytic
function. One powerful way of doing this is to choose structure neighbors from
phylogenetically distant organisms. We therefore need to combine our present search
with a Taxonomy search. Given that 1B8G is derived from the superkingdom Eukaryota,
we would like to find structure neighbors in other superkingdom taxa, such as Eubacteria
and Archaea. Returning to the Structure Summary page, select the 3D Domains link in
the graphic display to open the list of 3D Domains in Entrez. Finding 1B8GA3 in the list,
selecting the Related 3D Domains link shows a list of all the structure neighbors of this
domain. From this page, we select Preview/Index , which shows our recent queries.
Suppose our set of related 3D Domains is #5. We then perform two searches:
1. #5 AND “Archaea”[Organism]
2. #5 AND “Eubacteria”[Organism]
Looking at the Archaea results, we find among them 1DJUA3, a domain from an
aromatic aminotransferase from Pyrococcus horikoshii . Concerning the Eubacteria
results, we find among the several hundred matching domains 3TATA2, a tyrosine
aminotransferase from Escherichia coli .
Viewing a 3D Superposition of Active Sites. Returning to the VAST Structure
Neighbors page for 1B8GA3, we want to select 1DJUA3 and 3TATA2 to display in a
structural alignment. One way to do this is to enter these two Accession numbers in the
Find box and press Find . We now see only these two neighbors, and we can select View
3D Structure to launch Cn3D.
Cn3D again displays the aligned residues in red, and we can highlight these
further by selecting Show aligned residues from the Show/Hide menu. The excellent
agreement between both the active site structures and the conformations of the bound
ligands is readily apparent. Furthermore, by selecting Style/Coloring Shortcuts/Sequence
Conservation/Variety , we can easily see that the most highly conserved residues are
concentrated near the binding site (Figure 6).