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Computational Design of Peptide Inhibitor Based on Modifications of Proregion from Plutella xylostella Midgut Trypsin
Author(s) -
Jitonnom Jitrayut,
Lomthaisong Khemika,
Lee Vannajan S.
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2011.01312.x
Subject(s) - plutella , midgut , protease , trypsin , proteases , diamondback moth , biochemistry , docking (animal) , in silico , peptide , peptide sequence , chemistry , amino acid , enzyme , biology , medicine , ecology , botany , lepidoptera genitalia , nursing , larva , gene
Many proteases are produced as zymogens bearing the N‐terminal proregions acting both as intramolecular chaperones and as protease inhibitors. The latter role of the proregions as potent and specific inhibitors of their associated protease has been demonstrated in various peptidases and therefore has been targeted for alternative pest control. Here, we isolated amino acid sequence of Plutella xylostella midgut trypsin from the larvae of diamondback moth and tested in silico for its inhibitory activity toward propeptide models using computational modeling and docking. The propeptide models (AAAPGHR, AAAPGRR, AAAPGKR, AAPGHRI, APGHRIV, PGHRIVG, AAAAPGH, and PG) were designed based on histidine‐mutated and frame‐shifted modifications of the 7‐amino‐acid proregion (AAAPGHR) of the Plutella xylostella trypsin. Among the eight peptides, AAAPGRR was found to give the best docking scores, showing a strong binding to the cognate enzyme. In addition, the obtained structure of trypsin–AAAPGRR complex was found to share a similar binding mode with a crystal structure of plant protease inhibitor complex. Our results may guide the experiment for the design of future peptide inhibitor with specificity and selectivity for the target enzyme.