Structural, functional, and inhibition studies of a Gcn5-related N-acetyltransferase (GNAT) superfamily protein PA4794: a new C-terminal lysine protein acetyltransferase from pseudomonas aeruginosa.

The Journal of Biological Chemistry
Karolina A MajorekWladek Minor

Abstract

The Gcn5-related N-acetyltransferase (GNAT) superfamily is a large group of evolutionarily related acetyltransferases, with multiple paralogs in organisms from all kingdoms of life. The functionally characterized GNATs have been shown to catalyze the transfer of an acetyl group from acetyl-coenzyme A (Ac-CoA) to the amine of a wide range of substrates, including small molecules and proteins. GNATs are prevalent and implicated in a myriad of aspects of eukaryotic and prokaryotic physiology, but functions of many GNATs remain unknown. In this work, we used a multi-pronged approach of x-ray crystallography and biochemical characterization to elucidate the sequence-structure-function relationship of the GNAT superfamily member PA4794 from Pseudomonas aeruginosa. We determined that PA4794 acetylates the Nε amine of a C-terminal lysine residue of a peptide, suggesting it is a protein acetyltransferase specific for a C-terminal lysine of a substrate protein or proteins. Furthermore, we identified a number of molecules, including cephalosporin antibiotics, which are inhibitors of PA4794 and bind in its substrate-binding site. Often, these molecules mimic the conformation of the acetylated peptide product. We have determined structures ...Continue Reading

References

Jun 30, 2000·Protein Expression and Purification·R B Kapust, D S Waugh
Aug 15, 2000·Annual Review of Biophysics and Biomolecular Structure·F DydaA B Hickman
May 5, 2004·Chemistry & Biology·Matthew W VettingJohn S Blanchard
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Sep 25, 2004·Acta Crystallographica. Section D, Biological Crystallography·Huanwang YangJohn D Westbrook
Nov 20, 2004·Molecular Pharmacology·Kyung-Tae ParkCornelis J Elferink
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Dec 8, 2004·Archives of Biochemistry and Biophysics·Matthew W VettingJohn S Blanchard
Mar 12, 2005·Journal of the American Academy of Dermatology·Arash Izadpanah, Richard L Gallo
Apr 9, 2005·The Journal of Biological Chemistry·Matthew W VettingJohn S Blanchard
Dec 24, 2005·Journal of Synchrotron Radiation·Gerd RosenbaumAndrzej Joachimiak
Jul 21, 2006·Acta Crystallographica. Section D, Biological Crystallography·Wladek MinorMaksymilian Chruszcz
Apr 25, 2007·Nucleic Acids Research·Ian W DavisDavid C Richardson
Jul 4, 2008·Protein Science : a Publication of the Protein Society·Matthew W VettingJohn S Blanchard
Aug 30, 2008·Molecular & Cellular Proteomics : MCP·Junmei ZhangYingming Zhao
May 29, 2009·The Journal of Biological Chemistry·Michael M BrentRonen Marmorstein
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
May 12, 2010·Nucleic Acids Research·Liisa Holm, Päivi Rosenström
May 22, 2010·Molecular Microbiology·Linda I HuAlan J Wolfe
Feb 8, 2011·PloS One·Martin MalmstenArtur Schmidtchen
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
Nov 28, 2012·Protein Science : a Publication of the Protein Society·Misty L KuhnWayne F Anderson
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Jan 1, 2014·Expert Opinion on Drug Discovery·Heping ZhengWladek Minor
Jan 29, 2016·Biochemistry·Lorenza FavrotOlivia Vergnolle
Mar 21, 2015·Food Microbiology·Laurel S BurallAtin R Datta
May 26, 2016·Journal of Proteomics·Takfarinas KentacheJulie Hardouin
Jul 2, 2016·International Journal of Molecular Sciences·Abu Iftiaf Md Salah Ud-DinAnna Roujeinikova
Dec 4, 2012·Molecular Cell·Joshua C BlackJohnathan R Whetstine
Jun 30, 2015·Experimental Hematology·Chun-Wei Chen, Scott A Armstrong
Jul 22, 2014·Protein Science : a Publication of the Protein Society·Karolina A MajorekWladek Minor
Jan 28, 2015·Journal of Molecular Biology·Ekaterina V FilippovaWayne F Anderson
Jul 10, 2019·Acta Crystallographica. Section F, Structural Biology Communications·John T LazarGeorge Minasov
Apr 22, 2014·The Journal of Biological Chemistry·Marjetka PodobnikSandhya S Visweswariah
Jul 14, 2017·Scientific Reports·Pu RenLei Xue
Apr 21, 2018·Nature Protocols·Katarzyna B HandingWladek Minor
Apr 17, 2017·Biochemical and Biophysical Research Communications·Sungwook Shin, Jungwoo Choe
Apr 8, 2021·Protein Science : a Publication of the Protein Society·Van Thi Bich LeMisty L Kuhn
Apr 30, 2021·Frontiers in Molecular Biosciences·Jackson T BaumgartnerMisty L Kuhn

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