Reverse transcriptase domains

Warner N, Locamini S, Kuiper M, Bartholomeusz A, Ayres A, Yuen L, Shaw T (2007) The L80I substitution in the reverse transcriptase domain of the hepatitis B virus polymerase is associated with lamivudine resistance and enhanced viral replication in vitro, Antimicrob Agents Chemother 51 2285-2292... 

Intron encoded maturases. These proteins, which are normally encoded by an open reading frame (ORF) within the intron, bind specifically their own RNA and promote formation of critical tertiary contacts. In addition, most of these proteins have endonuclease and reverse-transcriptase domains, which allow intron mobility (i.e., retrotransposition and retrohom-ing) by a mechanism termed target primed reverse transcription (TPRT) (vide infra). 

It is important to note that clusters that contain ESTs only (i.e., no mRNAs or armotated CDSs) will be missing some of these fields, such as LocusLink, OMIM, and mRNA/Gene links. UniGene titles for such clusters, such as EST, weakly similar to ORE2 contains a reverse transcriptase domain [H. sapiens], are derived from the title of a characterized protein with which the translated EST sequence aligns. The cluster title might be as simple as EST if the ESTs share no significant similarity with characterized proteins. 

Studies using free energy calculations for the design and analysis of potential drug candidates are reviewed in section five. The chapters in this section cover drug discovery programs targeting fructose 1,6-bisphosphatase (diabetes), COX-2 (inflammation), SRC SH2 domain (osteoporosis and cancer), HIV reverse transcriptase (AIDS), HIV-1 protease (AIDS), thymidylate synthase (cancer), dihydrofolate reductase (cancer) and adenosine deaminase (immunosuppression, myocardial ischemia). 

Divalent metal ions are essential for ribonuclease H activity. Two Mn(II) ions have been located in the catalytic site of ribonuclease H domain of HIV-1 reverse transcriptase in close proximity to the four acidic residues Asp443, Glu478, Asp498, and Asp549 after soaking crystals in 45 mM MnCl2 (406). 

The catalytic core domain of HIV-1 integrase has a topologically identical fold with the RNase H domain of HIV-1 reverse transcriptase [37], the RuvC Holli-... 

Tanese N, Goff SP. Domain structure of the Moloney murine leukemia virus reverse transcriptase mutational analysis and separate expression of the DNA polymerase and RNase H activities. Proc Natl Acad Sci USA 1988 85 1777-1781. 

Tisdale M, Schulze T, Larder BA, Moelling K. Mutations within the RNase H domain of human immunodeficiency virus type 1 reverse transcriptase abolish virus infectivity. J Gen Virol 1991 72 59-66. 

Davies JF, Hostomska Z, Hostomsky Z, Jordan SR, Matthews DA. Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. Science 1991 252 88-95. 

Schatz O, Cromme FV, Gmninger-Leitch F, Le Grice SFJ. Point mutations in conserved amino acid residues within the C-terminal domain of HIV-1 reverse transcriptase specifically repress RNase H function. FEBS Lett 1989 257 311-314. 

Mizrahi V, Brooksbank RL, Nkabinde NC. Mutagenesis of the conserved aspartic acid 443, glutamic acid 478, asparagine 494, and aspartic acid 498 residues in the ribonuclease H domain of p66/p51 human immunodeficiency vims type 1 reverse transcriptase. JBiol Chem 1994 269 19245-19249. 

Other DNA polymerases. Reverse transcriptases synthesize DNA using an RNA template strand. They are best known for their function in retroviruses (Chapter 28). The HIV reverse transcriptase is a heterodimer of 51- and 66-kDa subunits. The larger subunit contains a ribonuclease H domain.288-2893 The enzyme is a prime target for drugs such as AZT and others.290 291 A different reverse transcriptase is found in all eukaryotic cells in telom-erase, an enzyme essential for replication of chromosome ends. Reverse transcriptases have also been found in rare LI sequences that are functioning ret-rotransposons (Section D).292... 

Fig. 2. Structures of family A, B, X, Y, and RT polymerases. The proteins are in ribbon representation. The fingers, palm, and thumb subdomains are color-coded in gold, red, and green, respectively. (A) Structure of apo Klentaql (family A). The 3 -5 vestigial exonuclease domain is indicated in silver. (B) Structure of apo RB69 DNA polymerase (family B). The 3 -5 exonuclease domain and the N-terminal domain are indicated in grey and silver, respectively. (C) Structure of apo pol / DNA polymerase (family X). The lyase domain is indicated grey. (D) Structure of the Dpo4 DNA polymerase (family Y). The litde finger subdomain is indicated in silver. (E) Structure of the p66 subunit of reverse transcriptase (RT family). The RNAseH and connection subdomains are indicated in grey and silver, respectively.

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