The cyclic dipeptide CI-4 [cyclo-(l-Arg-d-Pro)] inhibits family 18 chitinases by structural mimicry of a reaction intermediate.
نویسندگان
چکیده
Family 18 chitinases are attractive targets for the development of new inhibitors with chemotherapeutic potential against fungi, insects and protozoan/nematodal parasites. Although several inhibitors have been identified, these are based on complex chemistry, which hampers iterative structure-based optimization. Here we report the details of chitinase inhibition by the natural product peptide CI-4 [ cyclo -(L-Arg-D-Pro)], which possesses activity against the human pathogenic fungus Candida albicans, and describe a 1.7 A (0.17 nm) crystal structure of CI-4 in complex with the enzyme. The structure reveals that the cyclic dipeptide inhibits chitinases by structurally mimicking a reaction intermediate, and could, on the basis of its accessible chemistry, be a candidate for further optimization.
منابع مشابه
Structure-based exploration of cyclic dipeptide chitinase inhibitors.
Family 18 chitinases play an essential role in a range of pathogens and pests. Several inhibitors are known, including the potent inhibitors argadin and allosamidin, and the structures of these in complex with chitinases have been elucidated. Recent structural analysis has revealed that CI-4 [cyclo-(L-Arg-D-Pro)] inhibits family 18 chitinases by mimicking the structure of the proposed reaction ...
متن کاملA novel chitinase inhibitor from a marine bacterium, Pseudomonas sp.
A new chitinase inhibitor, CI-4, was isolated from the culture broth of a marine bacterium Pseudomonas sp. IZ208. The structure of CI-4 was determined to be cyclo(L-Arg-D-Pro) by spectral studies and comparison with a synthetic sample. CI-4 showed inhibitory activity against chitinase.
متن کاملThe effect of chitinase inhibitors, cyclo(Arg-Pro) against cell separation of Saccharomyces cerevisiae and the morphological change of Candida albicans.
In a previous paperX), we reported a new chitinase inhibitor, cyclo(L-Arg-D-Pro) from marine bacteria. At the budding cell stage of Saccharomyces cerevisiae, chitin is known to be a main constituent of the primary septum between the mother and daughter cells2). Amongthe chitin metabolite enzymes, chitin synthase is essential for the septum formation3). It is known that polyoxin D inhibits chiti...
متن کاملSynthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres.
A set of cyclic peptide analogues of a selective CXCR4 antagonist FC131 [cyclo(-d-Tyr-Arg-Arg-Nal-Gly-)] were synthesized and bioevaluated. Using (E)-alkene and (Z)-fluoroalkene dipeptide isosteres for Arg-Arg and Arg-Nal substructures, indispensable or the partial contribution of the two peptide bonds to the CXCR4 antagonism and anti-HIV activity was demonstrated. FC131 and the analogues were ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Biochemical journal
دوره 368 Pt 1 شماره
صفحات -
تاریخ انتشار 2002