title: Functional implications of the modeled structure of maspin.
abstract: The tumor suppressor maspin (mammary-specific serpin) is an unstable serpin that does not undergo the stressed to relaxed transition typical of proteinase inhibitory serpins and, consequently, is not likely to function as a serine proteinase inhibitor. This suggests that the positioning and configuration of the reactive site loop (RSL) of maspin are likely to resemble those of ovalbumin, the best studied non-inhibitory serpin. Accordingly, the tertiary structure of maspin has been modeled on the crystal structure of native ovalbumin. Biochemical data and the modeled theoretical structure of maspin reveal the absence of disulfide bonds in the molecule and the presence of an unstable RSL that adopts a distorted helical structure. We confirm that the RSL is extremely sensitive to limited proteolysis and suggest that this may provide a structural basis for the proteolytic inactivation of maspin, a process that is likely to modulate the activity of maspin in biological systems.
authors.affiliation: LXR Biotechnology, Richmond, CA 94804, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Fitzpatrick
authors.forename: D T
authors.initials: DT
authors.lastname: Wong
authors.forename: P J
authors.initials: PJ
authors.lastname: Barr
authors.forename: P A
authors.initials: PA
authors.lastname: Pemberton
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D016147:Genes, Tumor Suppressor; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000737:chemistry; D010446:Peptide Fragments / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D015843:Serpins / Q000737:chemistry* / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D011506:Proteins; D011994:Recombinant Proteins; C085344:SERPIN-B5; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D010047:Ovalbumin; D014357:Trypsin