title: The first structure in a family of peptidase inhibitors reveals an unusual Ig-like fold.
abstract: We report the crystal structure solution of the Intracellular Protease Inhibitor (IPI) protein from Bacillus subtilis, which has been reported to be an inhibitor of the intracellular subtilisin Isp1 from the same organism. The structure of IPI is a variant of the all-beta, immunoglobulin (Ig) fold. It is possible that IPI is important for protein-protein interactions, of which inhibition of Isp1 is one. The intracellular nature of ISP is questioned, because an alternative ATG codon in the ipi gene would produce a protein with an N-terminal extension containing a signal peptide. It is possible that alternative initiation exists, producing either an intracellular inhibitor or a secreted form that may be associated with the cell surface.  Homologues of the IPI protein from other species are multi-domain proteins, containing signal peptides and domains also associated with the bacterial cell-surface. The cysteine peptidase inhibitors chagasin and amoebiasin also have Ig-like folds, but their topology differs significantly from that of IPI, and they share no recent common ancestor. A model of IPI docked to Isp1 shows similarities to other subtilisin:inhibitor complexes, particularly where the inhibitor interacts with the peptidase active site.
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rigden
authors.affiliation: Joint Center for Structural Genomics, La Jolla CA, 92037, USA ; Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park CA, 94025, USA.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Sandford-Burnham Institute, La Jolla CA, 92037, USA.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK ; European Molecular Biology Laboratory, European Bioinformatics Institute,Wellcome Trust Genome Campus, Hinxton, CB10 1SD, UK.
authors.forename: Ruth Y
authors.initials: RY
authors.lastname: Eberhardt
authors.affiliation: Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn VA, 20147, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Finn
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK ; European Molecular Biology Laboratory, European Bioinformatics Institute,Wellcome Trust Genome Campus, Hinxton, CB10 1SD, UK.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Rawlings