IUBMB Enzyme Nomenclature

EC 3.1.26.13

Accepted name: retroviral ribonuclease H

Reaction: Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes:
1. sequence-specific internal cleavage of RNA [1-4]. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction [5].
2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end [6,7].
3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus [8-10].

Other name(s): RT/RNase H; retroviral reverse transcriptase RNaseH; HIV RNase H

Comments: Comments: Retroviral reverse transcriptase is a multifunctional enzyme responsible for viral replication. To perform this task the enzyme combines two distinct activities. The polymerase domain (EC 2.7.7.49, RNA-directed DNA polymerase) occupies the N-terminal two-thirds of the reverse transcriptase whereas the ribonuclease H domain comprises the C-terminal remaining one-third [13,14]. The RNase H domain of Moloney murine leukemia virus and Human immunodeficiency virus display two metal binding sites [15-17]

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:

References:

1. Schultz, S.J., Zhang, M. and Champoux, J.J. Recognition of internal cleavage sites by retroviral RNases H. J. Mol. Biol. 344 (2004) 635-652. [PMID: 15533434]

2. Sarafianos, S.G., Das, K., Tantillo, C., Clark, A.D., Jr., Ding, J., Whitcomb, J.M., Boyer, P.L., Hughes, S.H. and Arnold, E. Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA. EMBO J. 20 (2001) 1449-1461. [PMID: 11250910]

3. Rausch, J.W., Lener, D., Miller, J.T., Julias, J.G., Hughes, S.H. and Le Grice, S.F. Altering the RNase H primer grip of human immunodeficiency virus reverse transcriptase modifies cleavage specificity. Biochemistry 41 (2002) 4856-4865. [PMID: 11939780]

4. Brehm, J.H., Mellors, J.W. and Sluis-Cremer, N. Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Biochemistry 47 (2008) 14020-14027. [PMID: 19067547]

5. Schultz, S.J., Zhang, M., Kelleher, C.D. and Champoux, J.J. Analysis of plus-strand primer selection, removal, and reutilization by retroviral reverse transcriptases. J. Biol. Chem. 275 (2000) 32299-32309. [PMID: 10913435]

6. DeStefano, J.J., Mallaber, L.M., Fay, P.J. and Bambara, R.A. Determinants of the RNase H cleavage specificity of human immunodeficiency virus reverse transcriptase. Nucleic Acids Res. 21 (1993) 4330-4338. [PMID: 7692401]

7. Kati, W.M., Johnson, K.A., Jerva, L.F. and Anderson, K.S. Mechanism and fidelity of HIV reverse transcriptase. J. Biol. Chem. 267 (1992) 25988-25997. [PMID: 1281479]

8. Palaniappan, C., Fuentes, G.M., Rodriguez-Rodriguez, L., Fay, P.J. and Bambara, R.A. Helix structure and ends of RNA/DNA hybrids direct the cleavage specificity of HIV-1 reverse transcriptase RNase H. J. Biol. Chem. 271 (1996) 2063-2070. [PMID: 8567660]

9. Fu, T.B. and Taylor, J. When retroviral reverse transcriptases reach the end of their RNA templates. J. Virol. 66 (1992) 4271-4278. [PMID: 1376369]

10. Beilhartz, G.L., Wendeler, M., Baichoo, N., Rausch, J., Le Grice, S. and Gotte, M. HIV-1 reverse transcriptase can simultaneously engage its DNA/RNA substrate at both DNA polymerase and RNase H active sites: implications for RNase H inhibition. J. Mol. Biol. 388 (2009) 462-474. [PMID: 19289131]

11. Huang, H., Chopra, R., Verdine, G.L. and Harrison, S.C. Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 282 (1998) 1669-1675. [PMID: 9831551]

12. Krug, M.S. and Berger, S.L. Ribonuclease H activities associated with viral reverse transcriptases are endonucleases. Proc. Natl. Acad. Sci. USA 86 (1989) 3539-3543. [PMID: 2471188]

13. Champoux, J.J. and Schultz, S.J. Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription. FEBS J. 276 (2009) 1506-1516. [PMID: 19228195]

14. Schultz, S.J. and Champoux, J.J. RNase H activity: structure, specificity, and function in reverse transcription. Virus Res 134 (2008) 86-103. [PMID: 18261820]

15. Goedken, E.R. and Marqusee, S. Metal binding and activation of the ribonuclease H domain from moloney murine leukemia virus. Protein Eng. 12 (1999) 975-980. [PMID: 10585503]

16. Davies, J.F., 2nd, Hostomska, Z., Hostomsky, Z., Jordan, S.R. and Matthews, D.A. Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. Science 252 (1991) 88-95. [PMID: 1707186]

17. Pari, K., Mueller, G.A., DeRose, E.F., Kirby, T.W. and London, R.E. Solution structure of the RNase H domain of the HIV-1 reverse transcriptase in the presence of magnesium. Biochemistry 42 (2003) 639-650. [PMID: 12534276]

[EC 3.1.26.13 created 2009]


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