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To test this idea, we decided to calculate the propensity of hinges to occur in specific bins
of conservation score, for the 94 proteins in the Hinge Atlas with CSA annotation, rather
than for the larger set of 214. For this set we also found that hinge residues occur more
frequently among the 20% least conserved residues for each protein (Figure 2.6, Table
2.5). At a p-value of 0.003, the confidence in this result is high.
Even this test, however pools together hinges that are near the active site (or contain one
or more active site residues) with hinges that occur at some distance from it. So we
selected from the 94 proteins a small set that had at least one active site residue in the
hinge, and removed the active site residues themselves. We then calculated the
propensity of hinge residues to occur in the five conservation bins. This set was found to
be too small, however, and statistical significance was too low to draw a conclusion (data
not shown). A study using the set of fragment hinge motions described earlier was
similarly inconclusive.
The hypermutability of hinge residues that we found is reasonable because hinge residues
tend to be on the surface of proteins (see below) rather than in the more highly conserved
core. Hinges are less likely to be buried inside domains because they would then be
highly coordinated with near neighbors and hence less flexible. The apparent
contradiction of hypermutability on the one hand and enrichment of active sites on the
other is dealt with in the Discussion section. This result suggests mutagenesis is not a
helpful experimental tool for probing the hinge location.
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