Map discontinuities

A number of sharp edges can be seen in the Figure 5.4(b); these correspond to discontinuities in the mapping (in Figure 5.3, and see explanation in Figure 5.2). All but one of the six discontinuities with a map distance greater than 5 occur at the carboxy-termini of the strand residues, shown in pink in Figure 5.5. The majority of TIM-barrel proteins are enzymes, and the active site is always found at the carboxy-end of the $\beta$ -strands. Structural studies[Urfer & Kirschner, 1992, and references therein] suggest that the helix-loop-strand units (at the amino-terminus of the barrel) are more conserved and important for stabilisation of the fold, than the strand-loop-helix units at the opposite (active-site) end of the barrel. It is interesting that the discontinuities in the mapping of 1ghsA0 are at the less-stable end of the $\beta$ -strands, and that the more structurally important residues are not interrupted by discontinuities. Examination of seven other TIM-barrel domains (1pii01, 1amg01, 1llo00, 1ads00, 1tpfA0, 1nal10, and 1xyzA0) chosen objectively showed that this observation was part of a general trend. Discontinuities may be forced to occur where fewer (stabilising) inter-residue contacts are made. The residues identified by this method may be suitable points for the insertion of motifs or domains in the engineering of proteins with novel functions.

**Figure 5.4:** Distance matrices for domain 1ghsA0 calculated from (a) carbon- $\alpha$ coordinates and (b) intra-map distances (see text). All distances are Euclidean and normalised from white (closest) to black (furthest). The general pattern of contacts is mirrored in (a) and (b); the mapping preserves the majority of relative inter residue distances. The correlation coefficient between distances in (a) and (b) is 0.85. The discontinuities in (b) are discussed in the text and Figure 5.5.
$\begin{figure}\begin{center} \par (a) \mbox{\hspace{\onetoapage}}\\ \par\epsfig{file=chap5/figs/struct/dm_1ghsA0.eps,width=4in}(b) \par\end{center}\end{figure}$

**Figure 5.5:** Mapping discontinuities for domain 1ghsA0. Chain-breaking discontinuities (map distance units) in the mapping of this domain (see Figures 5.3 and 5.4) are shown in pink. Note that 5 out of 6 discontinuities are at the carboxy-terminus of the core $\beta$ -strands (see text for discussion).
$\begin{figure}\begin{center} \par\epsfig{file=chap5/figs/struct/1ghsA0_discont.ps,width=\onetoapage}\par\end{center}\end{figure}$