User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

Structural insights into the catalytic mechanism of a sacrificial sulfur insertase of the N-type ATP pyrophosphatase family, LarE.

Primary tabs

download
  • Open access
  • PDF
  • 1.73 M
Fellner, Matthias Desguin, Benoît [UCL] Hausinger, Robert P Hu, Jian

The lar operon in Lactobacillus plantarum encodes five Lar proteins (LarA/B/C/D/E) that collaboratively synthesize and incorporate a niacin-derived Ni-containing cofactor into LarA, an Ni-dependent lactate racemase. Previous studies have established that two molecules of LarE catalyze successive thiolation reactions by donating the sulfur atom of their exclusive cysteine residues to the substrate. However, the catalytic mechanism of this very unusual sulfur-sacrificing reaction remains elusive. In this work, we present the crystal structures of LarE in ligand-free and several ligand-bound forms, demonstrating that LarE is a member of the N-type ATP pyrophosphatase (PPase) family with a conserved N-terminal ATP PPase domain and a unique C-terminal domain harboring the putative catalytic site. Structural analysis, combined with structure-guided mutagenesis, leads us to propose a catalytic mechanism that establishes LarE as a paradigm for sulfur transfer through sacrificing its catalytic cysteine residue.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2017
Language Anglais
Journal information "Proceedings of the National academy of sciences of the United States of America" - Vol. 114, p. 9074-9079 (2017)
Peer reviewed yes
Publisher National academy of sciences
issn 0027-8424
e-issn 1091-6490
Publication status Publié
Affiliation Michigan State University - Department of Biochemistry and Molecular Biology
Keywords ATP pyrophosphatase ; Lar protein ; catalysis ; crystal structure ; thiolation
Links
  1. Wiederstein Markus, Gruber Markus, Frank Karl, Melo Francisco, Sippl Manfred J., Structure-Based Characterization of Multiprotein Complexes, 10.1016/j.str.2014.05.005
  2. Desguin Benoît, Goffin Philippe, Viaene Eric, Kleerebezem Michiel, Martin-Diaconescu Vlad, Maroney Michael J., Declercq Jean-Paul, Soumillion Patrice, Hols Pascal, Lactate racemase is a nickel-dependent enzyme activated by a widespread maturation system, 10.1038/ncomms4615
  3. Madej Thomas, Lanczycki Christopher J., Zhang Dachuan, Thiessen Paul A., Geer Renata C., Marchler-Bauer Aron, Bryant Stephen H., MMDB and VAST+: tracking structural similarities between macromolecular complexes, 10.1093/nar/gkt1208
  4. Welin Martin, Lehtiö Lari, Johansson Andreas, Flodin Susanne, Nyman Tomas, Trésaugues Lionel, Hammarström Martin, Gräslund Susanne, Nordlund Pär, Substrate Specificity and Oligomerization of Human GMP Synthetase, 10.1016/j.jmb.2013.06.032
  5. Guillén Schlippe Yollete V., Hedstrom Lizbeth, A twisted base? The role of arginine in enzyme-catalyzed proton abstractions, 10.1016/j.abb.2004.09.018
  6. Chatterjee Abhishek, Abeydeera N. Dinuka, Bale Shridhar, Pai Pei-Jing, Dorrestein Pieter C., Russell David H., Ealick Steven E., Begley Tadhg P., Saccharomyces cerevisiae THI4p is a suicide thiamine thiazole synthase, 10.1038/nature10503
  7. Bojarová Pavla, Williams Spencer J, Sulfotransferases, sulfatases and formylglycine-generating enzymes: a sulfation fascination, 10.1016/j.cbpa.2008.06.018
  8. Zhang G., Mills D. A., Block D. E., Development of Chemically Defined Media Supporting High-Cell-Density Growth of Lactococci, Enterococci, and Streptococci, 10.1128/aem.01416-08
  9. Sparta Karine M., Krug Michael, Heinemann Udo, Mueller Uwe, Weiss Manfred S., XDSAPP2.0, 10.1107/s1600576716004416
  10. Battye T. Geoff G., Kontogiannis Luke, Johnson Owen, Powell Harold R., Leslie Andrew G. W., iMOSFLM: a new graphical interface for diffraction-image processing withMOSFLM, 10.1107/s0907444910048675
  11. Evans Philip R., Murshudov Garib N., How good are my data and what is the resolution?, 10.1107/s0907444913000061
  12. Desguin B., Zhang T., Soumillion P., Hols P., Hu J., Hausinger R. P., A tethered niacin-derived pincer complex with a nickel-carbon bond in lactate racemase, 10.1126/science.aab2272
  13. Adams Paul D., Afonine Pavel V., Bunkóczi Gábor, Chen Vincent B., Davis Ian W., Echols Nathaniel, Headd Jeffrey J., Hung Li-Wei, Kapral Gary J., Grosse-Kunstleve Ralf W., McCoy Airlie J., Moriarty Nigel W., Oeffner Robert, Read Randy J., Richardson David C., Richardson Jane S., Terwilliger Thomas C., Zwart Peter H., PHENIX: a comprehensive Python-based system for macromolecular structure solution, 10.1107/s0907444909052925
  14. Emsley P., Lohkamp B., Scott W. G., Cowtan K., Features and development ofCoot, 10.1107/s0907444910007493
  15. Pettersen Eric F., Goddard Thomas D., Huang Conrad C., Couch Gregory S., Greenblatt Daniel M., Meng Elaine C., Ferrin Thomas E., UCSF Chimera?A visualization system for exploratory research and analysis, 10.1002/jcc.20084
  16. de Beer Tjaart A. P., Berka Karel, Thornton Janet M., Laskowski Roman A., PDBsum additions, 10.1093/nar/gkt940
  17. Larkin M.A., Blackshields G., Brown N.P., Chenna R., McGettigan P.A., McWilliam H., Valentin F., Wallace I.M., Wilm A., Lopez R., Thompson J.D., Gibson T.J., Higgins D.G., Clustal W and Clustal X version 2.0, 10.1093/bioinformatics/btm404
  18. Huson Daniel H., Scornavacca Celine, Dendroscope 3: An Interactive Tool for Rooted Phylogenetic Trees and Networks, 10.1093/sysbio/sys062
  19. Biasini Marco, Bienert Stefan, Waterhouse Andrew, Arnold Konstantin, Studer Gabriel, Schmidt Tobias, Kiefer Florian, Cassarino Tiziano Gallo, Bertoni Martino, Bordoli Lorenza, Schwede Torsten, SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information, 10.1093/nar/gku340
  20. Xu Tao, Wodrich Matthew D., Scopelliti Rosario, Corminboeuf Clemence, Hu Xile, Nickel pincer model of the active site of lactate racemase involves ligand participation in hydride transfer, 10.1073/pnas.1616038114
  21. Zhang Xiaoyong, Chung Lung W., Alternative Mechanistic Strategy for Enzyme Catalysis in a Ni-Dependent Lactate Racemase (LarA): Intermediate Destabilization by the Cofactor, 10.1002/chem.201604893
  22. Wang Binju, Shaik Sason, The Nickel-Pincer Complex in Lactate Racemase Is an Electron Relay and Sink that acts through Proton-Coupled Electron Transfer, 10.1002/anie.201612065
  23. Boer Jodi L., Mulrooney Scott B., Hausinger Robert P., Nickel-dependent metalloenzymes, 10.1016/j.abb.2013.09.002
  24. Desguin Benoît, Soumillion Patrice, Hols Pascal, Hausinger Robert P., Nickel-pincer cofactor biosynthesis involves LarB-catalyzed pyridinium carboxylation and LarE-dependent sacrificial sulfur insertion, 10.1073/pnas.1600486113
  25. Andreeva A., Howorth D., Chandonia J.-M., Brenner S. E., Hubbard T. J. P., Chothia C., Murzin A. G., Data growth and its impact on the SCOP database: new developments, 10.1093/nar/gkm993
  26. Tesmer John J.G., Klem Thomas J., Deras Michael L., Davisson V. Jo, Smith Janet L., The crystal structure of GMP synthetase reveals a novel catalytic triad and is a structural paradigm for two enzyme families, 10.1038/nsb0196-74
Bibliographic reference Fellner, Matthias ; Desguin, Benoît ; Hausinger, Robert P ; Hu, Jian. Structural insights into the catalytic mechanism of a sacrificial sulfur insertase of the N-type ATP pyrophosphatase family, LarE.. In: Proceedings of the National academy of sciences of the United States of America, Vol. 114, p. 9074-9079 (2017)
Permanent URL http://hdl.handle.net/2078/191945