Computational design of new and recombinant selenoproteins

Abstract

Selenoproteins contain the 21th amino acid Selenocysteine, which is encoded by the STOP-codon UGA. For its insertion it requires a specific rhRNA sequence downstream the UGA-codon that forms a hairpin-like structure (called Sec insertion sequence (SECIS)). Selenoproteins have gained much interest recently since they are very important for human health. In contrast, very little is known about selenoproteins. For example, there is only one solved crystal structure available. One reason for this is that one is not able to produce enough amount of selenoproteins by using recombinant expression in a system like E.coli. The reason is that the insertion mechanisms are different between E.coli and eukaryotes. Thus, one has to redesign the human/mammalian selenoprotein for the expression in E.coli. In this paper, we introduce an polynomial-time algorithm for solving the computational problem involved in this design, and we present results for known selenoproteins. © Springer-Verlag 2004.