1.2 A crystal structure of the serine carboxyl proteinase pro-kumamolisin; structure of an intact pro-subtilase

Structure
Mireia Comellas-BiglerW Bode

Abstract

Kumamolisin, an extracellular proteinase derived from an acido/thermophilic Bacillus, belongs to the sedolisin family of endopeptidases characterized by a subtilisin-like fold and a Ser-Glu-Asp catalytic triad. In kumamolisin, the Asp82 carboxylate hydrogen bonds to Glu32-Trp129, which might act as a proton sink stabilizing the catalytic residues. The 1.2/1.3 A crystal structures of the Glu32-->Ala and Trp129-->Ala mutants show that both mutations affect the active-site conformation, causing a 95% activity decrease. In addition, the 1.2 A crystal structure of the Ser278-->Ala mutant of pro-kumamolisin was determined. The prodomain exhibits a half-beta sandwich core docking to the catalytic domain similarly as the equivalent subtilisin prodomains in their catalytic-domain complexes. This pro-kumamolisin structure displays, for the first time, the uncleaved linker segment running across the active site and connecting the prodomain with the properly folded catalytic domain. The structure strongly points to an initial intramolecular activation cleavage in subtilases, as presumed for pro-subtilisin and pro-furin.

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Citations

Dec 3, 2005·PLoS Pathogens·Philippa K HarrisMichael J Blackman
May 4, 2006·Journal of the American Chemical Society·Qin XuHong Guo
Apr 16, 2008·The Journal of Biological Chemistry·Adam A GolabekElizabeth Kida
Feb 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Michael GambleD Dafydd Jones
Sep 27, 2012·Biochemistry·Ashley B DaughertyStefan Lutz
Mar 27, 2010·The Biochemical Journal·Nathalie BeaufortViktor Magdolen
Nov 28, 2012·Biochemical Society Transactions·Maarten G K GhequireRené De Mot
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Jul 10, 2004·Structure·Alexander Wlodawer
Apr 17, 2007·Nature Structural & Molecular Biology·David CunninghamXiayang Qiu
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Oct 19, 2005·The Biochemical Journal·Sergey A ShiryaevAlex Y Strongin
Jan 15, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Misty L KuhnGuido Grandi
Jul 1, 2006·Journal of Chemical Theory and Computation·Ksenia BravayaAlexander Nemukhin

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