Characterization and functional analysis of the cis-autoproteolysis active center of glycosylasparaginase.

The Journal of Biological Chemistry
C GuanH Paulus

Abstract

Glycosylasparaginase is an N-terminal nucleophile hydrolase and is activated by intramolecular autoproteolytic processing. This cis-autoproteolysis possesses unique kinetics characterized by a reversible N-O acyl rearrangement step in the processing. Arg-180 and Asp-183, involved in binding of the substrate in the mature enzyme, are also involved in binding of free amino acids in the partially formed substrate pocket on certain mutant precursors. This binding site is sequestered in the wild-type precursor. Binding of free amino acids on mutant precursors can either inhibit or accelerate their processing, depending on the individual mutants and amino acids. The polypeptide sequence at the processing site, which is highly conserved, adopts a special conformation. Asp-151 is essential for maintaining this conformation, possibly by anchoring its side chain into the partially formed substrate pocket through interaction with Arg-180. The reactive nucleophile Thr-152 is activated not only by deprotonation by His-150 but also by interaction with Thr-170, suggesting a His-Thr-Thr active triad for the autoproteolysis.

References

Apr 1, 1978·European Journal of Biochemistry·T Vajda, T Szabó
Sep 22, 1966·Biochemical and Biophysical Research Communications·M MakinoI Yamashina
Jan 19, 1995·Nature·H J DugglebyP C Moody
Nov 4, 1994·Science·P E DawsonS B Kent
Nov 30, 1993·Biochemical and Biophysical Research Communications·A L Tarentino, T H Plummer
Aug 1, 1993·Journal of Bacteriology·J W Little
Aug 1, 1996·Nature·E SeemullerW Baumeister
Dec 1, 1995·Nature Structural Biology·C OinonenL Peltonen
Oct 6, 1997·The Journal of Peptide Research : Official Journal of the American Peptide Society·Y Shao, H Paulus

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Citations

May 2, 2002·Molecular Reproduction and Development·Leigh Ann BushCharles J Flickinger
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Andrew R BullerCraig A Townsend
Dec 22, 2011·The Journal of Biological Chemistry·Seiji NegoroYoshiki Higuchi
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·J S Rosenblum, G Blobel
Mar 29, 2014·Biochemistry·Amanda M Schalk, Arnon Lavie
Feb 22, 2008·Protein Science : a Publication of the Protein Society·Yixin Sun, Hwai-Chen Guo
Aug 31, 2000·Annual Review of Biochemistry·H Paulus
Aug 9, 2003·Structure·Xiaofeng QianHwai-Chen Guo
Nov 14, 1998·Journal of Molecular Biology·S H DoneR E Hubbard
Sep 19, 2002·The Journal of Biological Chemistry·Hideyuki Suzuki, Hidehiko Kumagai
Jun 11, 2005·The Journal of Biological Chemistry·Karolina MichalskaMariusz Jaskolski
Mar 23, 2019·Protein Science : a Publication of the Protein Society·Suchita Pande, Hwai-Chen Guo
Mar 13, 2008·The Journal of Biological Chemistry·Karolina MichalskaMariusz Jaskolski
Mar 25, 2014·The Journal of Biological Chemistry·Christos S Karamitros, Manfred Konrad
Nov 5, 1999·The Journal of Biological Chemistry·M T TeixeiraB Dujon
Nov 16, 2002·The Journal of Biological Chemistry·Yeming Wang, Hwai-Chen Guo
Oct 10, 2003·The Journal of Biological Chemistry·Jongchul YoonYoungsoo Kim
Jul 5, 2017·Frontiers in Microbiology·Putri D UtariWim J Quax
Nov 13, 2020·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Hideyuki SuzukiHidehiko Kumagai
Nov 26, 1999·Biochimica Et Biophysica Acta·N N Aronson

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