1R64

The 2.2 A crystal structure of Kex2 protease in complex with Ac-Arg-Glu-Lys-boroArg peptidyl boronic acid inhibitor

Summary for 1R64

• Entry DOI: 10.2210/pdb1r64/pdb
• Related PRD ID: PRD_000420
• Descriptor: Kexin, Ac-Arg-Glu-Lys-boroArg peptide inhibitor, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: kex2, kexin, protease, protein convertase, prohormone processing, proprotein convertase, subtilisin, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Cellular location: Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane protein: P13134
• Total number of polymer chains: 4
• Total formula weight: 108707.82

Authors

Holyoak, T.,Kettner, C.A.,Petsko, G.A.,Fuller, R.S.,Ringe, D. (deposition date: 2003-10-14, release date: 2004-03-09, Last modification date: 2024-10-16)

Primary citation

Holyoak, T.,Kettner, C.A.,Petsko, G.A.,Fuller, R.S.,Ringe, D.
Structural Basis for Differences in Substrate Selectivity in Kex2 and Furin Protein Convertases
Biochemistry, 43:2412-2421, 2004

PubMed 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 A resolution crystal structure of ssKex2 in complex with an Ac-Arg-Glu-Lys-Arg peptidyl boronic acid inhibitor (R = 19.7, R(free) = 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 P(2) and P(4) positions between Kex2 and furin and provide a structural rationale for the lack of P(6) recognition in Kex2. In addition, several monovalent cation binding sites are identified, and a mechanism of activation of Kex2 by potassium ion is proposed.

PubMed: 14992578
DOI: 10.1021/bi035849h

Experimental method

X-RAY DIFFRACTION (2.2 Å)