Structurally conserved regions

A sequence alignment establishes the correspondences between the amino adds in th unknown protein and the template protein (or proteins) from wliich it will be built. Th three-dimensional structures of two or more related proteins are conveniently divided int structurally conserved regions (SCRs) and structurally variable regions (SVRs). Ihe structural conserved regions correspond to those stretches of maximum sequence identity or sequenc... 

Backbone generation is the first step in building a three-dimensional model of the protein. First, it is necessary to find structurally conserved regions (SCR) in the backbone. Next, place them in space with an orientation and conformation best matching those of the template. Single amino acid exchanges are assumed not to affect the tertiary structure. This often results in having sections of the model compound that are unconnected. 

SCR (structurally conserved regions) sections of a biopolymer sequence that are identical to that of another sequence, for which there is a known three-dimensional structure... 

List of Abbreviations GPCRs, G-protein coupled receptors PDB, protein database SCRs, structurally conserved regions SVRs, structurally variable regions... 

However, in many cases the proteins considered in the analysis are very similar and show only little structural variation. In these cases a superimposition of structurally conserved regions with standard protein homology modeling tools has yielded satisfactory protein superimpositions suited for the GRID/PCA or GRID/ GPGA analysis [8,9,13,17]. 

B. Assignment of Structurally Conserved Regions (SCRs) and Loops... 

Figure 7. Alignment of the sequences of the serine pioteinases shown in Figure 6. TRP, CHT, ELA, and MCP correspond to trypsin, chymotrypsin, elastase, and mast-cell proteinase, respectively. The shaded texes designate identical or highly conserved residues, and the bold horizontal lines represent structurally-conserved regions of these proteins derived from the structural overlay presented in Figure 6.

As noted above, the core-framework of a protein contains "packed" secondary-structural elements and is free of loops. Since proteins within a given family possess the same tertiary-fold motif, mutations of residues in the core-framework tend to preserve the general features of the tertiary fold [20,23,24] as well as the physicochemical characteristics of the mutated amino acids [33]. Moreover, as the coreframework is highly hydrophobic, conservation of hydrophobic residues is expected and is indeed observed to be the case [33,34]. Figure 7 also demonstrates this point, where the hydrophobic residues located within the structurally-conserved regions (denoted by bold horizontal bars) are seen to be well conserved. 

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