Analysis of the Active Site Cysteine Residue of the Sacrificial Sulfur Insertase LarE from Lactobacillus plantarum

Biochemistry
Matthias FellnerRobert P Hausinger

Abstract

LarE from Lactobacillus plantarum is an ATP-dependent sulfur transferase that sacrifices its Cys176 sulfur atom to form a dehydroalanine (Dha) side chain during biosynthesis of the covalently linked nickel-pincer nucleotide (NPN) cofactor (pyridinium 3-thioamide-5-thiocarboxylic acid mononucleotide) of lactate racemase. Coenzyme A (CoA) stabilizes LarE and forms a CoA-Cys176 mixed disulfide with the protein. This study presents the crystal structure of the LarE/CoA complex, revealing protein interactions with CoA that mimic those for binding ATP. CoA weakly inhibits LarE activity, and the persulfide of CoA is capable of partially regenerating functional LarE from the Dha176 form of the protein. The physiological relevance of this cycling reaction is unclear. A new form of LarE was discovered, an NPN-LarE covalent adduct, explaining prior results in which activation of the lactate racemase apoprotein required only the isolated LarE. The crystal structure of the inactive C176A variant revealed a fold essentially identical to that of wild-type LarE. Additional active site variants of LarE were created and their activities characterized, with all LarE variants analyzed in terms of the structure. Finally, the L. plantarum LarE struc...Continue Reading

References

Apr 1, 1979·Analytical Biochemistry·P W RiddlesB Zerner
Mar 1, 1987·Analytical Biochemistry·S W EnglanderJ J Englander
Jan 1, 1987·Methods in Enzymology·J L Wood
Jul 10, 2001·The Journal of Biological Chemistry·E G MuellerC J Buck
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jul 28, 2006·Nature·Tomoyuki NumataOsamu Nureki
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
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·T Geoff G BattyeAndrew G W Leslie
Oct 28, 2011·Nature·Abhishek ChatterjeeTadhg P Begley
Nov 13, 2012·The Journal of Biological Chemistry·Omer Kabil, Ruma Banerjee
Jun 26, 2013·Acta Crystallographica. Section D, Biological Crystallography·Philip R Evans, Garib N Murshudov
Apr 9, 2014·Nature Communications·Benoît DesguinPascal Hols
May 15, 2015·Molecular BioSystems·Chung-Min ParkMing Xian
Aug 20, 2015·Critical Reviews in Biotechnology·Veeresh Juturu, Jin Chuan Wu
Apr 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Benoît DesguinRobert P Hausinger
Oct 5, 2016·Archives of Biochemistry and Biophysics·Ernesto CuevasantaBeatriz Alvarez
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yuchen LiuDieter Söll
Apr 26, 2017·Proceedings of the National Academy of Sciences of the United States of America·Minghao ChenYoshikazu Tanaka
Jun 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Simon ArragainBéatrice Golinelli-Pimpaneau
Aug 9, 2017·Proceedings of the National Academy of Sciences of the United States of America·Matthias FellnerJian Hu
Aug 24, 2017·FEMS Microbiology Reviews·Benoît DesguinPascal Hols
Jun 12, 2018·The Journal of Biological Chemistry·Benoît DesguinPatrice Soumillion
Jul 18, 2018·Current Opinion in Chemical Biology·Robert P HausingerJian Hu

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Citations

Feb 6, 2020·Protein Science : a Publication of the Protein Society·Marila Alfano, Christine Cavazza
Oct 20, 2020·ChemCatChem·Jorge NevarezRobert P Hausinger
Oct 24, 2020·Scientific Reports·Benoît DesguinPatrice Soumillion
Sep 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Joel A RankinRobert P Hausinger

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