2g8v Citations

Stepwise analyses of metal ions in RNase H catalysis from substrate destabilization to product release.

EMBO J 25 1924-33 (2006)
Related entries: 2g8f, 2g8h, 2g8i, 2g8k, 2g8u, 2g8w

Cited: 151 times
EuropePMC logo PMID: 16601679

Abstract

In two-metal catalysis, metal ion A has been proposed to activate the nucleophile and metal ion B to stabilize the transition state. We recently reported crystal structures of RNase H-RNA/DNA substrate complexes obtained at 1.5-2.2 Angstroms. We have now determined and report here structures of reaction intermediate and product complexes of RNase H at 1.65-1.85 Angstroms. The movement of the two metal ions suggests how they may facilitate RNA hydrolysis during the catalytic process. Firstly, metal ion A may assist nucleophilic attack by moving towards metal ion B and bringing the nucleophile close to the scissile phosphate. Secondly, metal ion B transforms from an irregular coordination in the substrate complex to a more regular geometry in the product complex. The exquisite sensitivity of Mg(2+) to the coordination environment likely destabilizes the enzyme-substrate complex and reduces the energy barrier to form product. Lastly, product release probably requires dissociation of metal ion A, which is inhibited by either high concentrations of divalent cations or mutation of an assisting protein residue.

Articles - 2g8v mentioned but not cited (5)

  1. Stepwise analyses of metal ions in RNase H catalysis from substrate destabilization to product release. Nowotny M, Yang W. EMBO J 25 1924-1933 (2006)
  2. Catalytic mechanism of RNA backbone cleavage by ribonuclease H from quantum mechanics/molecular mechanics simulations. Rosta E, Nowotny M, Yang W, Hummer G. J Am Chem Soc 133 8934-8941 (2011)
  3. Understanding the effect of magnesium ion concentration on the catalytic activity of ribonuclease H through computation: does a third metal binding site modulate endonuclease catalysis? Ho MH, De Vivo M, Dal Peraro M, Klein ML. J Am Chem Soc 132 13702-13712 (2010)
  4. Novel complex MAD phasing and RNase H structural insights using selenium oligonucleotides. Abdur R, Gerlits OO, Gan J, Jiang J, Salon J, Kovalevsky AY, Chumanevich AA, Weber IT, Huang Z. Acta Crystallogr D Biol Crystallogr 70 354-361 (2014)
  5. Controlled Trafficking of Multiple and Diverse Cations Prompts Nucleic Acid Hydrolysis. Manigrasso J, De Vivo M, Palermo G. ACS Catal 11 8786-8797 (2021)


Reviews citing this publication (36)

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  23. The hepatitis B virus ribonuclease H as a drug target. Tavis JE, Lomonosova E. Antiviral Res 118 132-138 (2015)
  24. Ca2+ versus Mg2+ coordination at the nucleotide-binding site of the sarcoplasmic reticulum Ca2+-ATPase. Picard M, Jensen AM, Sørensen TL, Champeil P, Møller JV, Nissen P. J Mol Biol 368 1-7 (2007)
  25. A Glimpse of "Dicer Biology" Through the Structural and Functional Perspective. Paturi S, Deshmukh MV. Front Mol Biosci 8 643657 (2021)
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Articles citing this publication (110)