title: Trypsin inhibition by a peptide hormone: crystal structure of trypsin-vasopressin complex.
abstract: The large variety of serine protease inhibitors, available from various sources such as tissues, microorganisms, plants, etc., play an important role in regulating the proteolytic enzymes. The analysis of protease-inhibitor complexes helps in understanding the mechanism of action, as well as in designing inhibitors. Vasopressin, an anti-diuretic nonapeptide hormone, is found to be an effective inhibitor of trypsin, with a K(i) value of 5 nM. The crystal structure of the trypsin-vasopressin complex revealed that vasopressin fulfils all the important interactions for an inhibitor, without any break in the scissile peptide bond. The cyclic nature due to a disulfide bridge between Cys1 and Cys6 of vasopressin provides structural rigidity to the peptide hormone. The trypsin-binding site is located at the C terminus, while the neurophysin-binding site is at the N terminus of vasopressin. This study will assist in designing new peptide inhibitors. This study suggests that vasopressin inhibition of trypsin may have unexplored biological implications.
authors.affiliation: Department of Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025, India.
authors.forename: B
authors.initials: B
authors.lastname: Syed Ibrahim
authors.forename: Vasantha
authors.initials: V
authors.lastname: Pattabhi
mesh_terms: D001665:Binding Sites; D003461:Crystallography; D006801:Humans; D015394:Molecular Structure; D014357:Trypsin / Q000737:chemistry* / Q000187:drug effects; D014361:Trypsin Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D014667:Vasopressins / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D014361:Trypsin Inhibitors; D014667:Vasopressins; D014357:Trypsin