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Structural insights into the Thermus thermophilus ADP-ribose pyrophosphatase mechanism via crystal structures with the bound substrate and metal.

Yoshiba S, Ooga T, Nakagawa N, Shibata T, Inoue Y, Yokoyama S, Kuramitsu S, Masui R
J Biol Chem 279 37163-74 (2004)
Related entries: 1v8i, 1v8l, 1v8m, 1v8n, 1v8r, 1v8t, 1v8u, 1v8v, 1v8w, 1v8y

Cited: 20 times
EuropePMC logo PMID: 15210687

Abstract

ADP-ribose pyrophosphatase (ADPRase) catalyzes the divalent metal ion-dependent hydrolysis of ADP-ribose to ribose 5'-phosphate and AMP. This enzyme plays a key role in regulating the intracellular ADP-ribose levels, and prevents nonenzymatic ADP-ribosylation. To elucidate the pyrophosphatase hydrolysis mechanism employed by this enzyme, structural changes occurring on binding of substrate, metal and product were investigated using crystal structures of ADPRase from an extreme thermophile, Thermus thermophilus HB8. Seven structures were determined, including that of the free enzyme, the Zn(2+)-bound enzyme, the binary complex with ADP-ribose, the ternary complexes with ADP-ribose and Zn(2+) or Gd(3+), and the product complexes with AMP and Mg(2+) or with ribose 5'-phosphate and Zn(2+). The structural and functional studies suggested that the ADP-ribose hydrolysis pathway consists of four reaction states: bound with metal (I), metal and substrate (II), metal and substrate in the transition state (III), and products (IV). In reaction state II, Glu-82 and Glu-70 abstract a proton from a water molecule. This water molecule is situated at an ideal position to carry out nucleophilic attack on the adenosyl phosphate, as it is 3.6 A away from the target phosphorus and almost in line with the scissile bond.

Reviews citing this publication (1)

  1. Structures and mechanisms of Nudix hydrolases. Mildvan AS, Xia Z, Azurmendi HF, Saraswat V, Legler PM, Massiah MA, Gabelli SB, Bianchet MA, Kang LW, Amzel LM. Arch Biochem Biophys 433 129-143 (2005)

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  4. Crystal structure of the 25 kDa subunit of human cleavage factor Im. Coseno M, Martin G, Berger C, Gilmartin G, Keller W, Doublié S. Nucleic Acids Res 36 3474-3483 (2008)
  5. Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity. Zha M, Zhong C, Peng Y, Hu H, Ding J. J Mol Biol 364 1021-1033 (2006)
  6. Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base. Nakamura T, Meshitsuka S, Kitagawa S, Abe N, Yamada J, Ishino T, Nakano H, Tsuzuki T, Doi T, Kobayashi Y, Fujii S, Sekiguchi M, Yamagata Y. J Biol Chem 285 444-452 (2010)
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  8. Ligand-induced activation of human TRPM2 requires the terminal ribose of ADPR and involves Arg1433 and Tyr1349. Fliegert R, Watt JM, Schöbel A, Rozewitz MD, Moreau C, Kirchberger T, Thomas MP, Sick W, Araujo AC, Harneit A, Potter BVL, Guse AH. Biochem J 474 2159-2175 (2017)
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  12. Structural basis for different substrate specificities of two ADP-ribose pyrophosphatases from Thermus thermophilus HB8. Wakamatsu T, Nakagawa N, Kuramitsu S, Masui R. J Bacteriol 190 1108-1117 (2008)
  13. Structural studies of the Nudix GDP-mannose hydrolase from E. coli reveals a new motif for mannose recognition. Boto AN, Xu W, Jakoncic J, Pannuri A, Romeo T, Bessman MJ, Gabelli SB, Amzel LM. Proteins 79 2455-2466 (2011)
  14. Structure and mechanism of the bifunctional CinA enzyme from Thermus thermophilus. Karuppiah V, Thistlethwaite A, Dajani R, Warwicker J, Derrick JP. J Biol Chem 289 33187-33197 (2014)
  15. Structural and Enzymatic Characterization of a Nucleoside Diphosphate Sugar Hydrolase from Bdellovibrio bacteriovorus. de la Peña AH, Suarez A, Duong-Ly KC, Schoeffield AJ, Pizarro-Dupuy MA, Zarr M, Pineiro SA, Amzel LM, Gabelli SB. PLoS One 10 e0141716 (2015)
  16. Visualization of mutagenic nucleotide processing by Escherichia coli MutT, a Nudix hydrolase. Nakamura T, Yamagata Y. Proc Natl Acad Sci U S A 119 e2203118119 (2022)
  17. Alr2954 of Anabaena sp. PCC 7120 with ADP-ribose pyrophosphatase activity bestows abiotic stress tolerance in Escherichia coli. Singh PK, Shrivastava AK, Singh S, Rai R, Chatterjee A, Rai LC. Funct Integr Genomics 17 39-52 (2017)
  18. Kinetic and mutational studies of the adenosine diphosphate ribose hydrolase from Mycobacterium tuberculosis. O'Handley SF, Thirawatananond P, Kang LW, Cunningham JE, Leyva JA, Amzel LM, Gabelli SB. J Bioenerg Biomembr 48 557-567 (2016)
  19. Letter Crystal Structures of Arabidopsis thaliana Nudix Hydrolase NUDT7 Reveal a Previously Unobserved Conformation. Tang Q, Liu C, Zhong C, Ding J. Mol Plant 8 1557-1559 (2015)


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