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Publication Abstract from PubMed

Protease inhibitors of the Bowman-Birk (BBI) family are commonly found in plants and animals where they play a protective role against invading pathogens. Here we report an atomic resolution (1A) crystal structure of a peptide inhibitor isolated from a skin secretion of a Chinese bamboo odorous frog Huia versabilis (HV-BBI) in complex with trypsin. HV-BBI shares significant similarities in sequence with a previously described inhibitor from a diskless-fingered odorous frog Odorrana graham (ORB). However, the latter is characterized by more than a 16000 fold higher Ki against trypsin than HV-BBI. Comparative analysis of trypsin co-crystal structures of HV-BBI and ORB and additionally that of Sunflower Trypsin Inhibitor (SFTI-1) together with accessory information on the affinities of inhibitor variants allowed us to pinpoint the inhibitor moiety responsible for the observed large difference in activity and also to define the extent of modifications permissible within the common protease-binding loop scaffold of BBI inhibitors. We suggest that modifications outside of the inhibitory loop permit the evolution of specificity towards different enzymes characterized by trypsin-like specificity. This article is protected by copyright. All rights reserved.

Atomic resolution crystal structure of HV-BBI protease inhibitor from amphibian skin in complex with bovine trypsin.,Grudnik P, Debowski D, Legowska A, Malicki S, Golik P, Karna N, Rolka K, Dubin G Proteins. 2014 Dec 24. doi: 10.1002/prot.24750. PMID:25546528^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.