1OT5

The 2.4 Angstrom Crystal Structure of Kex2 in complex with a peptidyl-boronic acid inhibitor

Summary for 1OT5

• Entry DOI: 10.2210/pdb1ot5/pdb
• Related PRD ID: PRD_000411
• Descriptor: Kexin, Ac-Ala-Lys-boroArg N-acetylated boronic acid peptide inhibitor, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: subtilisin fold, peptidyl-boronic acid, serine protease, p-domain, hydrolase, 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: 106699.26

Authors

Holyoak, T.,Wilson, M.A.,Fenn, T.D.,Kettner, C.A.,Petsko, G.A.,Fuller, R.S.,Ringe, D. (deposition date: 2003-03-21, release date: 2003-06-17, Last modification date: 2024-10-30)

Primary citation

Holyoak, T.,Wilson, M.A.,Fenn, T.D.,Kettner, C.A.,Petsko, G.A.,Fuller, R.S.,Ringe, D.
2.4 A Resolution Crystal Structure of the Prototypical Hormone-Processing Protease Kex2 in Complex with an Ala-Lys-Arg Boronic Acid Inhibitor
Biochemistry, 42:6709-6718, 2003

PubMed Abstract: This paper reports the first structure of a member of the Kex2/furin family of eukaryotic pro-protein processing proteases, which cleave sites consisting of pairs or clusters of basic residues. Reported is the 2.4 A resolution crystal structure of the two-domain protein ssKex2 in complex with an Ac-Ala-Lys-boroArg inhibitor (R = 20.9%, R(free) = 24.5%). The Kex2 proteolytic domain is similar in its global fold to the subtilisin-like superfamily of degradative proteases. Analysis of the complex provides a structural basis for the extreme selectivity of this enzyme family that has evolved from a nonspecific subtilisin-like ancestor. The P-domain of ssKex2 has a novel jelly roll like fold consisting of nine beta strands and may potentially be involved, along with the buried Ca(2+) ion, in creating the highly determined binding site for P(1) arginine.

PubMed: 12779325
DOI: 10.1021/bi034434t

Experimental method

X-RAY DIFFRACTION (2.4 Å)