KEGG   ENZYME: 3.1.26.13Help
Entry
EC 3.1.26.13                Enzyme                                 

Name
retroviral ribonuclease H;
RT/RNase H;
retroviral reverse transcriptase RNaseH;
HIV RNase H
Class
Hydrolases;
Acting on ester bonds;
Endoribonucleases producing 5'-phosphomonoesters
BRITE hierarchy
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
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]
History
EC 3.1.26.13 created 2009
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 (2004) 635-52.
  Organism
Human immunodeficiency virus
  Sequence
[up:P03366]
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 (2001) 1449-61.
  Organism
Human immunodeficiency virus
  Sequence
[up:P03366]
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 (2002) 4856-65.
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 (2008) 14020-7.
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 (2000) 32299-309.
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 (1993) 4330-8.
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 (1992) 25988-97.
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 (1996) 2063-70.
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 (1992) 4271-8.
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 (2009) 462-74.
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 (1998) 1669-75.
  Organism
Human immunodeficiency virus
  Sequence
[up:P03366]
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 (1989) 3539-43.
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 (2009) 1506-16.
Reference
14 [PMID:18261820]
  Authors
Schultz SJ, Champoux JJ
  Title
RNase H activity: structure, specificity, and function in reverse transcription.
  Journal
Virus. Res. 134 (2008) 86-103.
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 (1999) 975-80.
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 (1991) 88-95.
  Organism
Human immunodeficiency virus
  Sequence
[up:P03366]
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 (2003) 639-50.
  Organism
Human immunodeficiency virus
  Sequence
[up:P04585]
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
CAS: 
9050-76-4

DBGET integrated database retrieval system