The F-helix of serpins plays an essential, active role in the proteinase inhibition mechanism.
Proteinase inhibition by serpins requires a 70 A translocation of the proteinase, circumvention of the blocking helix F, and a crushing of the proteinase to render it catalytically incompetent. I propose that temporary displacement of the F-helix during proteinase transit, and its subsequent return after complete passage of the proteinase, not only allows the proteinase to reach its final location, but provides an absolutely essential coupling mechanism for making the final proteinase crushing step energetically favorable. The F-helix is therefore not a passive impediment to proteinase translocation, but a critical, active element in permitting the serpin inhibition mechanism to operate successfully.
Department of Biochemistry and Molecular Biology, College of Medicine, University of Illinois at Chicago, 60612-4316, Chicago, IL, USA. pgettins@uic.edu
Peter G W
PG
Gettins
D010450:Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D008958:Models, Molecular; D017433:Protein Structure, Secondary / Q000502:physiology; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D015843:Serpins / Q000737:chemistry* / Q000494:pharmacology; D013816:Thermodynamics
D015842:Serine Proteinase Inhibitors; D015843:Serpins; D010450:Endopeptidases