Structural Basis for Differences in Substrate Selectivity in Kex2 and Furin Protein Convertases,
- 10 February 2004
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 43 (9) , 2412-2421
- https://doi.org/10.1021/bi035849h
Abstract
Kex2 is the yeast prototype of a large family of serine proteases that are highly specific for cleavage of their peptide substrates C-terminal to paired basic sites. This paper reports the 2.2 Å resolution crystal structure of ssKex2 in complex with an Ac-Arg-Glu-Lys-Arg peptidyl boronic acid inhibitor (R = 19.7, Rfree = 23.4). By comparison of this structure with the structure of the mammalian homologue furin [Henrich, S., et al. (2003) Nat. Struct. Biol. 10, 520−526], we suggest a structural basis for the differences in substrate recognition at the P2 and P4 positions between Kex2 and furin and provide a structural rationale for the lack of P6 recognition in Kex2. In addition, several monovalent cation binding sites are identified, and a mechanism of activation of Kex2 by potassium ion is proposed.Keywords
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