Structural basis for the substrate specificity of PepA from Streptococcus pneumoniae, a dodecameric tetrahedral protease

Biochemical and Biophysical Research Communications
Doyoun KimKyeong Kyu Kim

Abstract

Regulated cytosolic proteolysis is one of the key cellular processes ensuring proper functioning of a cell. M42 family proteases show a broad spectrum of substrate specificities, but the structural basis for such diversity of the substrate specificities is lagging behind biochemical data. Here we report the crystal structure of PepA from Streptococcus pneumoniae, a glutamyl aminopeptidase belonging to M42 family (SpPepA). We found that Arg-257 in the substrate binding pocket is strategically positioned so that Arg-257 can make electrostatic interactions with the acidic residue of a substrate at its N-terminus. Structural comparison of the substrate binding pocket of the M42 family proteases, along with the structure-based multiple sequence alignment, argues that the appropriate electrostatic interactions contribute to the selective substrate specificity of SpPepA.

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Citations

Nov 8, 2015·Biochimie·Alexandre AppolaireBruno Franzetti
Apr 8, 2014·Biochemical and Biophysical Research Communications·Duy Duc NguyenKyeong Kyu Kim
Nov 1, 2016·ACS Applied Materials & Interfaces·Boi Hoa SanKyeong Kyu Kim
Jun 6, 2018·Journal of Bacteriology·Hind BasbousBruno Franzetti
Feb 9, 2016·Scientific Reports·Matteo ColomboBruno Franzetti
Sep 4, 2013·Acta Crystallographica. Section D, Biological Crystallography·Hai Minh TaKyeong Kyu Kim
Mar 14, 2013·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Boi Hoa SanKyeong Kyu Kim
Nov 6, 2014·Acta Crystallographica. Section D, Biological Crystallography·Alexandre AppolaireFrank Gabel
May 25, 2013·Chemistry, an Asian Journal·Takafumi UenoYuya Tanaka
May 28, 2019·Frontiers in Molecular Biosciences·Björn RichtsFabian M Commichau
Oct 16, 2019·The Journal of Biological Chemistry·Raphaël DutoitLouis Droogmans
May 23, 2013·The Journal of Biological Chemistry·Alexandre AppolaireBruno Franzetti
Jul 4, 2018·Chemical Reviews·Toktam NezakatiAlexander M Seifalian
Nov 19, 2021·Frontiers in Cellular and Infection Microbiology·Murtadha Q AliSven Hammerschmidt

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