Protein homologs, divergent

The most straightforward method for comparison of 3-D structures involves rigid-body least-squares superposition of the C positions. We have developed a procedure for alignment of several homologous structures [9, 10] without bias to any one in the set. Divergent proteins usually retain the general arrangement of strands and helices. However, when there are less than 20% sequence identities, the differences in relative orientation and position of the secondary structural elements usually preclude their simultaneous superposition [1,2,11,12). 

Placer DA et al. A novel and highly divergent homolog of human eosinophil granule major basic protein. J Biol Chem 1999 274 14464-14473. 

In general, the 10 different forms of adenylyl cyclase can be divided into three major and two minor groups based on their functional attributes as well as on their sequence homology. The three major families are (1) the Ca2+/calmodulin-stimulated isoforms, which include AC1, AC3, and AC8 certain of these enzymes are inhibited by GPt (2) the G[ -stimulated isoforms, which include AC2, AC4, and AC7 and (3) the Ca2+ and Gai inhibited isoforms, which are AC5 and AC6. The other two categories each have a single member (4) AC9, which is the most divergent of the membrane-bound isoforms, is stimulated by G(IS, inhibited by calcineurin (a protein phosphatase), and is insensitive to forskolin (5) sAC, the only soluble isoform, is the most divergent and is most similar to the adenylyl cyclase found in Cyanobacteria. 

Experience gained from protein structure determination in the past 30 years demonstrates that domains possessing similar sequences also possess similar folds, leading to the inference that such domains are members of homologous families (Doolittle, 1995 Henikoff etal., 1997). Some homologous domain sequences have diverged considerably beyond the level at which homology can be reliably predicted. However,... 

---