KEGG   ENZYME: 3.1.26.13
Entry
EC 3.1.26.13                Enzyme                                 
Name
retroviral ribonuclease H;
RT/RNase H;
retroviral reverse transcriptase RNaseH (gene name);
HIV RNase H
Class
Hydrolases;
Acting on ester bonds;
Endoribonucleases producing 5'-phosphomonoesters
Reaction(IUBMB)
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].
Comment
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 domains of Moloney murine leukemia virus and Human immunodeficiency virus display two metal binding sites [15-17]
History
EC 3.1.26.13 created 2009
Orthology
K24802  HIV-1 reverse transcriptase / ribonuclease H
Reference
1  [PMID:15533434]
  Authors
Schultz SJ, Zhang M, Champoux JJ
  Title
Recognition of internal cleavage sites by retroviral RNases H.
  Journal
J Mol Biol 344:635-52 (2004)
DOI:10.1016/j.jmb.2004.09.081
Reference
2  [PMID:11250910]
  Authors
Sarafianos SG, Das K, Tantillo C, Clark AD Jr, Ding J, Whitcomb JM, Boyer PL, Hughes SH, Arnold E
  Title
Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA.
  Journal
EMBO J 20:1449-61 (2001)
DOI:10.1093/emboj/20.6.1449
Reference
3  [PMID:11939780]
  Authors
Rausch JW, Lener D, Miller JT, Julias JG, Hughes SH, Le Grice SF
  Title
Altering the RNase H primer grip of human immunodeficiency virus reverse transcriptase modifies cleavage specificity.
  Journal
Biochemistry 41:4856-65 (2002)
DOI:10.1021/bi015970t
Reference
4  [PMID:19067547]
  Authors
Brehm JH, Mellors JW, Sluis-Cremer N
  Title
Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance.
  Journal
Biochemistry 47:14020-7 (2008)
DOI:10.1021/bi8014778
Reference
5  [PMID:10913435]
  Authors
Schultz SJ, Zhang M, Kelleher CD, Champoux JJ
  Title
Analysis of plus-strand primer selection, removal, and reutilization by retroviral reverse transcriptases.
  Journal
J Biol Chem 275:32299-309 (2000)
DOI:10.1074/jbc.M000021200
Reference
6  [PMID:7692401]
  Authors
DeStefano JJ, Mallaber LM, Fay PJ, Bambara RA
  Title
Determinants of the RNase H cleavage specificity of human immunodeficiency virus  reverse transcriptase.
  Journal
Nucleic Acids Res 21:4330-8 (1993)
DOI:10.1093/nar/21.18.4330
Reference
7  [PMID:1281479]
  Authors
Kati WM, Johnson KA, Jerva LF, Anderson KS
  Title
Mechanism and fidelity of HIV reverse transcriptase.
  Journal
J Biol Chem 267:25988-97 (1992)
Reference
8  [PMID:8567660]
  Authors
Palaniappan C, Fuentes GM, Rodriguez-Rodriguez L, Fay PJ, Bambara RA
  Title
Helix structure and ends of RNA/DNA hybrids direct the cleavage specificity of HIV-1 reverse transcriptase RNase H.
  Journal
J Biol Chem 271:2063-70 (1996)
DOI:10.1074/jbc.271.4.2063
Reference
9  [PMID:1376369]
  Authors
Fu TB, Taylor J
  Title
When retroviral reverse transcriptases reach the end of their RNA templates.
  Journal
J Virol 66:4271-8 (1992)
DOI:10.1128/JVI.66.7.4271-4278.1992
Reference
10 [PMID:19289131]
  Authors
Beilhartz GL, Wendeler M, Baichoo N, Rausch J, Le Grice S, Gotte M
  Title
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.
  Journal
J Mol Biol 388:462-74 (2009)
DOI:10.1016/j.jmb.2009.03.025
Reference
11 [PMID:9831551]
  Authors
Huang H, Chopra R, Verdine GL, Harrison SC
  Title
Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance.
  Journal
Science 282:1669-75 (1998)
DOI:10.1126/science.282.5394.1669
Reference
12 [PMID:2471188]
  Authors
Krug MS, Berger SL
  Title
Ribonuclease H activities associated with viral reverse transcriptases are endonucleases.
  Journal
Proc Natl Acad Sci U S A 86:3539-43 (1989)
DOI:10.1073/pnas.86.10.3539
Reference
13 [PMID:19228195]
  Authors
Champoux JJ, Schultz SJ
  Title
Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription.
  Journal
FEBS J 276:1506-16 (2009)
DOI:10.1111/j.1742-4658.2009.06909.x
Reference
14 [PMID:18261820]
  Authors
Schultz SJ, Champoux JJ
  Title
RNase H activity: structure, specificity, and function in reverse transcription.
  Journal
Virus Res 134:86-103 (2008)
DOI:10.1016/j.virusres.2007.12.007
Reference
15 [PMID:10585503]
  Authors
Goedken ER, Marqusee S
  Title
Metal binding and activation of the ribonuclease H domain from moloney murine leukemia virus.
  Journal
Protein Eng 12:975-80 (1999)
DOI:10.1093/protein/12.11.975
Reference
16 [PMID:1707186]
  Authors
Davies JF 2nd, Hostomska Z, Hostomsky Z, Jordan SR, Matthews DA
  Title
Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase.
  Journal
Science 252:88-95 (1991)
DOI:10.1126/science.1707186
Reference
17 [PMID:12534276]
  Authors
Pari K, Mueller GA, DeRose EF, Kirby TW, London RE
  Title
Solution structure of the RNase H domain of the HIV-1 reverse transcriptase in the presence of magnesium.
  Journal
Biochemistry 42:639-50 (2003)
DOI:10.1021/bi0204894
Other DBs
ExplorEnz - The Enzyme Database: 3.1.26.13
IUBMB Enzyme Nomenclature: 3.1.26.13
ExPASy - ENZYME nomenclature database: 3.1.26.13
BRENDA, the Enzyme Database: 3.1.26.13
CAS: 9050-76-4

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