1O8Z
Solution structure of SFTI-1(6,5), an acyclic permutant of the proteinase inhibitor SFTI-1, cis-trans-trans conformer (ct-A)
Summary for 1O8Z
| Entry DOI | 10.2210/pdb1o8z/pdb |
| Related | 1JBL 1JBN 1O8Y 1SFI |
| Descriptor | CYCLIC TRYPSIN INHIBITOR (1 entity in total) |
| Functional Keywords | protease inhibitor, bowman-birk inhibitor, sfti-1, acyclic permutant |
| Biological source | HELIANTHUS ANNUUS L. (SUNFLOWER) |
| Total number of polymer chains | 1 |
| Total formula weight | 1535.83 |
| Authors | Marx, U.C.,Craik, D.J. (deposition date: 2002-12-09, release date: 2003-03-13, Last modification date: 2011-07-13) |
| Primary citation | Marx, U.C.,Korsinczky, M.,Schirra, H.,Jones, A.,Condie, B.,Otvos, L.,Craik, D.J. Enzymatic Cyclization of a Potent Bowman-Birk Protease Inhibitor, Sunflower Trypsin Inhibitor-1, and Solution Structure of an Acyclic Precursor Peptide J.Biol.Chem., 278:21782-, 2003 Cited by PubMed Abstract: The most potent known naturally occurring Bowman-Birk inhibitor, sunflower trypsin inhibitor-1 (SFTI-1), is a bicyclic 14-amino acid peptide from sunflower seeds comprising one disulfide bond and a cyclic backbone. At present, little is known about the cyclization mechanism of SFTI-1. We show here that an acyclic permutant of SFTI-1 open at its scissile bond, SFTI-1[6,5], also functions as an inhibitor of trypsin and that it can be enzymatically backbone-cyclized by incubation with bovine beta-trypsin. The resulting ratio of cyclic SFTI-1 to SFTI-1[6,5] is approximately 9:1 regardless of whether trypsin is incubated with SFTI-1[6,5] or SFTI-1. Enzymatic resynthesis of the scissile bond to form cyclic SFTI-1 is a novel mechanism of cyclization of SFTI-1[6,5]. Such a reaction could potentially occur on a trypsin affinity column as used in the original isolation procedure of SFTI-1. We therefore extracted SFTI-1 from sunflower seeds without a trypsin purification step and confirmed that the backbone of SFTI-1 is indeed naturally cyclic. Structural studies on SFTI-1[6,5] revealed high heterogeneity, and multiple species of SFTI-1[6,5] were identified. The main species closely resembles the structure of cyclic SFTI-1 with the broken binding loop able to rotate between a cis/trans geometry of the I7-P8 bond with the cis conformer being similar to the canonical binding loop conformation. The non-reactive loop adopts a beta-hairpin structure as in cyclic wild-type SFTI-1. Another species exhibits an iso-aspartate residue at position 14 and provides implications for possible in vivo cyclization mechanisms. PubMed: 12621047DOI: 10.1074/JBC.M212996200 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
