The 1.5 A crystal structure of a prokaryote serpin: controlling conformational change in a heated environment

Structure. 2003 Apr;11(4):387-97. doi: 10.1016/s0969-2126(03)00057-1.


Serpins utilize conformational change to inhibit target proteinases; the price paid for this conformational flexibility is that many undergo temperature-induced polymerization. Despite this thermolability, serpins are present in the genomes of thermophilic prokaryotes, and here we characterize the first such serpin, thermopin. Thermopin is a proteinase inhibitor and, in comparison with human alpha(1)-antitrypsin, possesses enhanced stability at 60 degrees C. The 1.5 A crystal structure reveals novel structural features in regions implicated in serpin folding and stability. Thermopin possesses a C-terminal "tail" that interacts with the top of the A beta sheet and plays an important role in the folding/unfolding of the molecule. These data provide evidence as to how this unusual serpin has adapted to fold and function in a heated environment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinomycetales / chemistry*
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Crystallography, X-Ray
  • Enzyme Stability
  • Hot Temperature*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation*
  • Protein Denaturation
  • Sequence Alignment
  • Serine Proteinase Inhibitors / chemistry*
  • Serine Proteinase Inhibitors / genetics
  • Serine Proteinase Inhibitors / metabolism
  • Serpins / chemistry*
  • Serpins / genetics
  • Serpins / metabolism
  • alpha 1-Antitrypsin / chemistry
  • alpha 1-Antitrypsin / genetics


  • Bacterial Proteins
  • Serine Proteinase Inhibitors
  • Serpins
  • alpha 1-Antitrypsin

Associated data

  • PDB/1MTP