Evolutionary relationships among the serpins

Abstract

The serpins are a widely distributed group of serine proteinase inhibitors found in plants, birds, mammals and viruses. Despite the great evolutionary divergence of these organisms, their serpins are highly conserved, both in sequence and structurally. Amino acid sequences were aligned by a combination of automatic algorithms and by consideration of conserved structural elements in those serpins for which crystal structures exist. The program HOMED was used which allowed the alignment of amino acids to be simultaneously converted into the equivalently aligned nucleotide sequences. The aligned amino acids were used as the basis for superposition of the four known three-dimensional structures for which coordinates are available and compared with an optimal three-dimensional superposition in order to estimate the reliability of the sequence alignment. Phylogenetic relationships implied by these nucleotide sequence alignments were determined by the method of maximum parsimony. The proposed gene tree suggested that as much diversity existed between the plant serpin and mammalian serpins as was present among mammalian serpins and provided further evidence that the architecture of serpin molecules is highly constrained.

Identification of a novel human serpin gene; cloning sequencing and expression of leupin

“…These key differences imply that leupin is not merely as isoform of SCCA, but is likely to have a different target protease or profile of target proteases. The two serpins represent a closer evolutionary divergence than previously seen in mammalian serpins which generally show 30-50% sequence identity [24], and must represent a relatively recent gene duplication event.…”

MSP22.8 is a protease inhibitor‐like protein involved in shell mineralization in the edible mussel Mytilus galloprovincialis

“…Electrophoretically some differences were found and these could be due to PTM or sugar moieties. In fact, serpins are mostly glycoproteins 34. Indeed, the apparent molecular mass of MSP22.8 (≈ 55 kDa) would be higher than the theoretical value reported for PILP‐B1 (≈ 43 kDa).…”

“…Serpins are a family of proteins that can function as serine proteinase inhibitors 32, 33. They are widely distributed and show a highly conserved structure and sequence 34. Although homology between members of the serpin family is poor, they do have a conserved core structure 35.…”

Inhibition of coagulation factors by recombinant barley serpin BSZx

“…The experiments with factor Xa illustrate that a large fraction of the serpin molecules may be cleaved as a substrate at the inhibitory site in accordance with the suicide inhibition scheme and the kinetic model. BSZx contains a potential substrate site at P6 Arg, a position generally occupied by a hydrophobic residue [1], but no cleavage at this site could be detected with any of the four coagulation factors.…”

“…Members of the serpin superfamily of se...£ine proteinase in....: hibitors have been identified in higher animals, insects, viruses and plants [1]. Most mammalian serpins function as regulators of complex physiological processes such as blood coagulation, fibrinolysis and complement activation [2,3] whereas little is known about the biological activity and function of serpins from plants.…”