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Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

Emergence and evolutionary connections between enzymatic functions via prototypes of elementary functional loops

Earlier studies of protein structure revealed closed loops with a characteristic size 25-30 residues and ring-like shape as a basic universal structural element of globular proteins (1,2). Elementary functional loops (EFL) have specific signatures and provide functional residues important for binding/activation and principal chemical transformation steps of the enzymatic reaction (3). We derive prototypes of the elementary functional loops (EFLs) and use them for dissecting the enzymatic function into its building blocks. As a result, previously uncharted evolutionary connections between seemingly unrelated enzymes become apparent. We show that proteins with different folds and biochemical reactions are built from limited set of common elementary functions (3).

We study relations between enzymatic functions in Archaeal superkingdom, using elementary functional loops (EFLs). Connections between different superfamilies and folds indicate events of EFLs’ recombination in the process of emergence of new biochemical functions. We also consider methanogenesis, a metabolic pathway typical for Archaea, as a case study of enzymes with specific biochemical functions and unique cofactors. We show that some methanogenic enzymes reutilize already existing folds with tuned original functions, while other methanogenic functions are apparently built de novo from EFLs. Examples of common elementary functions and role of corresponding EFLs as basic units of enzymes is discussed.

References

  1. I.N. Berezovsky, A.Y. Grosberg, E.N. Trifonov, FEBS Letters 466, 283-286 (2000).
  2. E.N. Trifonov, I.N. Berezovsky, Curr. Opin. Struct. Biol. 13, 110-114 (2003).
  3. A. Goncearenco, I.N. Berezovsky, Bioinformatics 26, i497-i503 (2010).

Alexander Goncearenco
and Igor N. Berezovsky

Computational Biology Unit and Department of Informatics, University of Bergen, Bergen, Norway

Phone: +47-55584712
Fax: +47-55584295
E-mail: Igor.Berezovsky@uni.no