5dqv › Citations

Structural and biochemical characterization of bacterial YpgQ protein reveals a metal-dependent nucleotide pyrophosphohydrolase.

Jeon YJ, Park SC, Song WS, Kim OH, Oh BC, Yoon SI
J Struct Biol 195 113-22 (2016)
Related entries: 5dqw, 5ihy

Cited: 15 times
EuropePMC logo PMID: 27062940

Abstract

The optimal balance of cellular nucleotides and the efficient elimination of non-canonical nucleotides are critical to avoiding erroneous mutation during DNA replication. One such mechanism involves the degradation of excessive or abnormal nucleotides by nucleotide-hydrolyzing enzymes. YpgQ contains the histidine-aspartate (HD) domain that is involved in the hydrolysis of nucleotides or nucleic acids, but the enzymatic activity and substrate specificity of YpgQ have never been characterized. Here, we unravel the catalytic activity and structural features of YpgQ to report the first Mn(2+)-dependent pyrophosphohydrolase that hydrolyzes (deoxy)ribonucleoside triphosphate [(d)NTP] to (deoxy)ribonucleoside monophosphate and pyrophosphate using the HD domain. YpgQ from Bacillus subtilis (bsYpgQ) displays a helical structure and assembles into a unique dimeric architecture that has not been observed in other HD domain-containing proteins. Each bsYpgQ monomer accommodates a metal ion and a nucleotide substrate in a cavity located between the N- and C-terminal lobes. The metal cofactor is coordinated by the canonical residues of the HD domain, namely, two histidine residues and two aspartate residues, and is positioned in close proximity to the β-phosphate group of the nucleotide, allowing us to propose a nucleophilic attack mechanism for the nucleotide hydrolysis reaction. YpgQ enzymes from other bacterial species also catalyze pyrophosphohydrolysis but exhibit different substrate specificity. Comparative structural and mutational studies demonstrated that residues outside the major substrate-binding site of bsYpgQ are responsible for the species-specific substrate preference. Taken together, our structural and biochemical analyses highlight the substrate-recognition mode and catalysis mechanism of YpgQ in pyrophosphohydrolysis.

Articles - 5dqv mentioned but not cited (2)

  1. The HD-Domain Metalloprotein Superfamily: An Apparent Common Protein Scaffold with Diverse Chemistries. Langton M, Sun S, Ueda C, Markey M, Chen J, Paddy I, Jiang P, Chin N, Milne A, Pandelia ME. Catalysts 10 1191 (2020)
  2. Structure of Ddi2, a highly inducible detoxifying metalloenzyme from Saccharomyces cerevisiae. Li J, Jia Y, Lin A, Hanna M, Chelico L, Xiao W, Moore SA. J Biol Chem 294 10674-10685 (2019)


Reviews citing this publication (1)

  1. Mechanisms supporting aminoadenine-based viral DNA genomes. Kaminski PA. Cell Mol Life Sci 79 51 (2021)

Articles citing this publication (12)

  1. An HD domain phosphohydrolase active site tailored for oxetanocin-A biosynthesis. Bridwell-Rabb J, Kang G, Zhong A, Liu HW, Drennan CL. Proc Natl Acad Sci U S A 113 13750-13755 (2016)
  2. Structural basis of effector and operator recognition by the phenolic acid-responsive transcriptional regulator PadR. Park SC, Kwak YM, Song WS, Hong M, Yoon SI. Nucleic Acids Res 45 13080-13093 (2017)
  3. Short- and Long-Term Effects of UVA on Arabidopsis Are Mediated by a Novel cGMP Phosphodiesterase. Isner JC, Olteanu VA, Hetherington AJ, Coupel-Ledru A, Sun P, Pridgeon AJ, Jones GS, Oates M, Williams TA, Maathuis FJM, Kift R, Webb AR, Gough J, Franklin KA, Hetherington AM. Curr Biol 29 2580-2585.e4 (2019)
  4. A tandem motif-based and structural approach can identify hidden functional phosphodiesterases. Kwiatkowski M, Wong A, Kozakiewicz A, Gehring C, Jaworski K. Comput Struct Biotechnol J 19 970-975 (2021)
  5. Metal-dependent SpoIIE oligomerization stabilizes FtsZ during asymmetric division in Bacillus subtilis. Cendrowicz E, de Sousa Borges A, Kopacz M, Scheffers DJ. PLoS One 12 e0174713 (2017)
  6. Crystal structure of the hydroxylaminopurine resistance protein, YiiM, and its putative molybdenum cofactor-binding catalytic site. Namgung B, Kim JH, Song WS, Yoon SI. Sci Rep 8 3304 (2018)
  7. Characterization of Runella slithyformis HD-Pnk, a Bifunctional DNA/RNA End-Healing Enzyme Composed of an N-Terminal 2',3'-Phosphoesterase HD Domain and a C-Terminal 5'-OH Polynucleotide Kinase Domain. Munir A, Shuman S. J Bacteriol 199 e00739-16 (2017)
  8. In Search of Monocot Phosphodiesterases: Identification of a Calmodulin Stimulated Phosphodiesterase from Brachypodium distachyon. Kwiatkowski M, Wong A, Kozakiewicz-Piekarz A, Gehring C, Jaworski K. Int J Mol Sci 22 9654 (2021)
  9. DNA processing by the MOBH family relaxase TraI encoded within the gonococcal genetic island. Heilers JH, Reiners J, Heller EM, Golzer A, Smits SHJ, van der Does C. Nucleic Acids Res 47 8136-8153 (2019)
  10. Functionally comparable but evolutionarily distinct nucleotide-targeting effectors help identify conserved paradigms across diverse immune systems. Nicastro GG, Burroughs AM, Iyer LM, Aravind L. Nucleic Acids Res 51 11479-11503 (2023)
  11. Recombinant Protein Expression, Crystallization, and Biophysical Studies of a Bacillus-conserved Nucleotide Pyrophosphorylase, BcMazG. Kim MI, Lee C, Hong M. J Vis Exp (2017)
  12. Structure-Function Analysis of the Phosphoesterase Component of the Nucleic Acid End-Healing Enzyme Runella slithyformis HD-Pnk. Munir A, Shuman S. J Bacteriol 201 e00292-19 (2019)


Quick links