Structural basis for substrate-specific acetylation of Nα-acetyltransferase Ard1 from Sulfolobus solfataricus

Scientific Reports
Yu-Yung Chang, Chun-Hua Hsu

Abstract

Nα-acetyltransferases (Nats) possess a wide range of important biological functions. Their structures can vary according to the first two residues of their substrate. However, the mechanisms of substrate recognition and catalysis of Nats are elusive. Here, we present two structure of Sulfolobus solfataricus Ard1 (SsArd1), a member of the NatA family, at 2.13 and 1.84 Å. Both structures contain coenzyme A, while the latter also contains a substrate-derived peptide. Sequential structure-based mutagenesis revealed that mutations of critical residues for CoA binding decreased the binding affinity of SsArd1 by 3 ~ 7-fold. Superimposition of SsArd1 (NatA) with human Naa50p (NatE) showed significant differences in key residues of enzymes near the first amino-acid position of the substrate peptide (Glu35 for SsArd1 and Val29 for Naa50p). Further enzyme activity assays revealed that the substrate specificity of SsArd1 could be altered from SSGTPT to MEEKVG by a range of Glu35 mutants. These studies provide not only a molecular elucidation of substrate recognition and specificity for the NatA family, but also insight into how members of the NAT family distinguish between amino acids at the substrate N-terminus from the ancient monomeric ...Continue Reading

References

Aug 15, 2000·Annual Review of Biophysics and Biomolecular Structure·F DydaA B Hickman
Oct 3, 2000·The Journal of Biological Chemistry·B Polevoda, F Sherman
Jan 1, 2003·Journal of Molecular Biology·Bogdan Polevoda, Fred Sherman
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 8, 2004·Archives of Biochemistry and Biophysics·Matthew W VettingJohn S Blanchard
Feb 4, 2006·Proceedings of the National Academy of Sciences of the United States of America·Maria C BewleyJohn M Flanagan
Dec 21, 2007·Acta Crystallographica. Section D, Biological Crystallography·Fei LongGarib N Murshudov
Jul 4, 2008·Protein Science : a Publication of the Protein Society·Matthew W VettingJohn S Blanchard
May 8, 2009·Proceedings of the National Academy of Sciences of the United States of America·Thomas ArnesenKris Gevaert
Aug 8, 2009·BMC Proceedings·Kristian K StarheimThomas Arnesen
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Jan 30, 2010·Science·Cheol-Sang HwangAlexander Varshavsky
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
May 12, 2010·Nucleic Acids Research·Liisa Holm, Päivi Rosenström
Oct 5, 2010·Archaea : an International Microbiological Journal·Jörg Soppa
Jun 3, 2011·Protein Science : a Publication of the Protein Society·Alexander Varshavsky
Jun 10, 2011·PLoS Biology·Gabriella M A ForteColin J Stirling
Aug 6, 2013·Nature Structural & Molecular Biology·Glen LiszczakRonen Marmorstein
May 16, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mingwei SunGeorge F Gao
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Feb 11, 2016·Scientific Reports·Om Singh RathoreRui Gonçalo Martinho
Jun 18, 2016·Proteins·Byron H YoungChristopher E Berndsen
Nov 3, 2016·Molecular & Cellular Proteomics : MCP·Egor A VorontsovJulia Chamot-Rooke
Nov 26, 2015·Chembiochem : a European Journal of Chemical Biology·Yu-Yung Chang, Chun-Hua Hsu
Dec 10, 2017·Oncotarget·Jing ChenJianhua Chen
Aug 12, 2020·Chemical Communications : Chem Comm·Yu-Yung ChangChun-Hua Hsu
Mar 25, 2020·Computational and Structural Biotechnology Journal·Angèle AbboudNathalie Reuter
Jan 17, 2021·Protein Science : a Publication of the Protein Society·Woo Suk ChoiWei Yang
Apr 17, 2017·Biochemical and Biophysical Research Communications·Sungwook Shin, Jungwoo Choe

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Methods Mentioned

BETA
acetylation
X-ray
acetylates
PCR
size-exclusion chromatography

Software Mentioned

BLAST
BALBES
SigmaPlot
PHENIX
MOLPROBITY
Coot
REFMAC5
HKL
PROCHECK
2000

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