1ha9
From Proteopedia
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SOLUTION STRUCTURE OF THE SQUASH TRYPSIN INHIBITOR MCOTI-II, NMR, 30 STRUCTURES.
Overview
The "knottin" fold is a stable cysteine-rich scaffold, in which one, disulfide crosses the macrocycle made by two other disulfides and the, connecting backbone segments. This scaffold is found in several protein, families with no evolutionary relationships. In the past few years, several homologous peptides from the Rubiaceae and Violaceae families were, shown to define a new structural family based on macrocyclic knottin fold., We recently isolated from Momordica cochinchinensis seeds the first known, macrocyclic squash trypsin inhibitors. These compounds are the first, members of a new family of cyclic knottins. In this paper, we present NMR, structural studies of one of them, MCoTI-II, and of a beta-Asp rearranged, form, MCoTI-IIb. Both compounds display similar and well-defined, conformations. These cyclic squash inhibitors share a similar conformation, with noncyclic squash inhibitors such as CPTI-II, and it is postulated, that the main effect of the cyclization is a reduced sensitivity to, exo-proteases. On the contrary, clear differences were detected with the, three-dimensional structures of other known cyclic knottins, i.e., kalata, B1 or circulin A. The two-disulfide cystine-stabilized beta-sheet motif, [Heitz et al. (1999) Biochemistry 38, 10615-10625] is conserved in the two, families, whereas in the C-to-N linker, one disulfide bridge and one loop, are differently located. The molecular surface of MCoTI-II is almost, entirely charged in contrast to circulin A that displays a well-marked, amphiphilic character. These differences might explain why the isolated, macrocyclic squash inhibitors from M. cochinchinensis display no, significant antibacterial activity, whereas circulins and kalata B1 do.
About this Structure
1HA9 is a Single protein structure of sequence from Momordica cochinchinensis. Full crystallographic information is available from OCA.
Reference
Solution structure of the squash trypsin inhibitor MCoTI-II. A new family for cyclic knottins., Heitz A, Hernandez JF, Gagnon J, Hong TT, Pham TT, Nguyen TM, Le-Nguyen D, Chiche L, Biochemistry. 2001 Jul 10;40(27):7973-83. PMID:11434766
Page seeded by OCA on Tue Nov 20 16:28:57 2007
