1o8y
From Proteopedia
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SOLUTION STRUCTURE OF SFTI-1(6,5), AN ACYCLIC PERMUTANT OF THE PROTEINASE INHIBITOR SFTI-1, TRANS-TRANS-TRANS CONFORMER (TT-A)
Overview
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.
About this Structure
1O8Y is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Enzymatic cyclization of a potent bowman-birk protease inhibitor, sunflower trypsin inhibitor-1, and solution structure of an acyclic precursor peptide., Marx UC, Korsinczky ML, Schirra HJ, Jones A, Condie B, Otvos L Jr, Craik DJ, J Biol Chem. 2003 Jun 13;278(24):21782-9. Epub 2003 Mar 5. PMID:12621047
Page seeded by OCA on Sun Nov 25 00:33:37 2007
