Sequence families

ZT Zhang. Relations of the numbers of protein sequences, families and folds. Protein Eng 10 757-761, 1997. 

Oliveira, L Paiva, A. C., and Vriend, G. (2002) Correlated mutation analysis on very large sequence families. Chembiochem 3,1010-1017. 

The use of sequence information to frame structural, functional, and evolutionary hypotheses represents a major challenge for the postgeno-mic era. Central to an understanding of the evolution of sequence families is the concept of the domain a structurally conserved, genetically mobile unit. When viewed at the three-dimensional level of protein structure, a domain is a compact arrangement of secondary structures connected by linker polypeptides. It usually folds independently and possesses a relatively hydrophobic core (Janin and Chothia, 1985). The importance of domains is that they cannot be divided into smaller units— they represent a fundamental building block that can be used to understand the evolution of proteins. 

This chapter anticipates the completion of Arabidopsis thaliana, Drosophila melanogaster, and Homo sapiens genome sequencing projects by reviewing current ideas of the evolution of sequence families. In parallel the related issue of domain homolog detection is discussed in light of continuing efforts to map the complete set of domain families. 

Wootton, J.C., Nicolson, R.E., Cock, J.M., Walters, D.E., Burke, J.F., Doyle, W.A. Bray, R.C. (1991). Enzymes depending on the pterin molybdenum cofactor sequence families, spectroscopic properties of molybdenum and possible cofactor-binding domains. Bio-chimica et Biophysica Acta 1057, 157-85. 

The rate of hybridization of repetitive human DNA suggested the existence of a single major repetitive DNA sequence family, a prediction... 

Andreeva, A., Howorth, D., Brenner, S.E., Hubbard, T.J., Chothia, C. and Murzin, A.G. (2004) SCOP database in 2004 refinements integrate stmcture and sequence family data. Nucleic Acids Res. 32, D226-D229. 

Despite these advances, Oberai et al. (3) estimate that if no acceleration of membrane protein structure determination occurs, then it will take more than three decades to determine at least one structural representative of 90% of the a-helical membrane protein sequence families (3). 

The generalisation that all members of the same CAZy sequence family adopt the same protein fold holds for CBMs in addition to hydrolases. However, the absolute correlation between CAZy sequence family and mechanism that holds for the glycohydrolases breaks down for CBMs. 

All Type B function is associated with a p-sandwich fold, but not all p-sandwich folds are associated with Type B function. The p-sandwich fold is adopted by CAZy sequence Families 2, 3,4, 6, 9,11,15,17,22,27,28,29, 32, 34 and 36, but some CAZy Family 2 members (CBM 2a) and all CBM Family 3 members have Type A function. In CBM 2a and CBM 3, three aromatic residues are again disposed to make a planar hydrophobic face sheet, as with CBM 1, even though the overall fold is a p-sandwich. The multiplicity of binding functions that can be supported by the p-sandwich is emphasised from the structure of a CBM6 attached to a Clostridium thermocellum xylanase, which had two binding clefts, only one of which appeared to be used in xylan binding the apparently unused cleft in this structure was, however, the main binding site for a Family 22 and a Family 4 module. ... 

Secondary structure prediction assigns a local helical (alpha) or extended (beta) structure to amino acid chains. The problem has been approached in an ab initio manner [46-48] for some time and many prediction methods have been developed based on properties of amino acids. Major advances have been achieved by employing homology-based approaches to 2D prediction. Such methods using sequence family information or consensus formation from several prediction methods are discussed in Section 6.4.1. 

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