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Active site plasticity revealed from the structure of the enterobacterial N-ribohydrolase RihA bound to a competitive inhibitor.

Garau G, Muzzolini L, Tornaghi P, Degano M
BMC Struct Biol 10 14 (2010)
Cited: 6 times
EuropePMC logo PMID: 20529317

Abstract

Background

Pyrimidine-preferring N-ribohydrolases (CU-NHs) are a class of Ca2+-dependent enzymes that catalyze the hydrolytic cleavage of the N-glycosidic bond in pyrimidine nucleosides. With the exception of few selected organisms, their physiological relevance in prokaryotes and eukaryotes is yet under investigation.

Results

Here, we report the first crystal structure of a CU-NH bound to a competitive inhibitor, the complex between the Escherichia coli enzyme RihA bound to 3, 4-diaminophenyl-iminoribitol (DAPIR) to a resolution of 2.1 A. The ligand can bind at the active site in two distinct orientations, and the stabilization of two flexible active site regions is pivotal to establish the interactions required for substrate discrimination and catalysis.

Conclusion

A comparison with the product-bound RihA structure allows a rationalization of the structural rearrangements required for an enzymatic catalytic cycle, highlighting a substrate-assisted cooperative motion, and suggesting a yet overlooked role of the conserved His82 residue in modulating product release. Differences in the structural features of the active sites in the two homologous CU-NHs RihA and RihB from E. coli provide a rationale for their fine differences in substrate specificity. These new findings hint at a possible role of CU-NHs in the breakdown of modified nucleosides derived from RNA molecules.

Reviews - 3g5i mentioned but not cited (1)

  1. Ribonucleoside Hydrolases-Structure, Functions, Physiological Role and Practical Uses. Shaposhnikov LA, Savin SS, Tishkov VI, Pometun AA. Biomolecules 13 1375 (2023)

Articles - 3g5i mentioned but not cited (2)

  1. Active site plasticity revealed from the structure of the enterobacterial N-ribohydrolase RihA bound to a competitive inhibitor. Garau G, Muzzolini L, Tornaghi P, Degano M. BMC Struct Biol 10 14 (2010)
  2. Structure-Functional Examination of Novel Ribonucleoside Hydrolase C (RihC) from Limosilactobacillus reuteri LR1. Shaposhnikov LA, Chikurova NY, Atroshenko DL, Savin SS, Kleymenov SY, Chernobrovkina AV, Pometun EV, Minyaev ME, Matyuta IO, Hushpulian DM, Boyko KM, Tishkov VI, Pometun AA. Int J Mol Sci 25 538 (2023)


Reviews citing this publication (1)

  1. Structure, Oligomerization and Activity Modulation in N-Ribohydrolases. Degano M. Int J Mol Sci 23 2576 (2022)

Articles citing this publication (2)

  1. Structure and function of nucleoside hydrolases from Physcomitrella patens and maize catalyzing the hydrolysis of purine, pyrimidine, and cytokinin ribosides. Kopecná M, Blaschke H, Kopecny D, Vigouroux A, Koncitíková R, Novák O, Kotland O, Strnad M, Moréra S, von Schwartzenberg K. Plant Physiol 163 1568-1583 (2013)
  2. A riboside hydrolase that salvages both nucleobases and nicotinamide in the auxotrophic parasite Trichomonas vaginalis. Patrone M, Galasyn GS, Kerin F, Nyitray MM, Parkin DW, Stockman BJ, Degano M. J Biol Chem 299 105077 (2023)


Related citations provided by authors (2)

  1. New insights into the mechanism of nucleoside hydrolases from the crystal structure of the Escherichia coli YbeK protein bound to the reaction product.. Muzzolini L, Versées W, Tornaghi P, Van Holsbeke E, Steyaert J, Degano M Biochemistry 45 773-82 (2006)
  2. Crystal structure to 1.7 a of the Escherichia coli pyrimidine nucleoside hydrolase YeiK, a novel candidate for cancer gene therapy.. Giabbai B, Degano M Structure 12 739-49 (2004)

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