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Journal ArticleDOI

A sequence motif in many polymerases.

11 Nov 1988-Nucleic Acids Research (Oxford University Press)-Vol. 16, Iss: 21, pp 9909-9916
TL;DR: A 15-residue sequence motif has been found in many polymerases from various species and involving DNA and RNA dependence and product and may be important in polymerase function by acting directly in catalysis and/or by binding magnesium.
Abstract: A 15-residue sequence motif has been found in many polymerases from various species and involving DNA and RNA dependence and product. The motif is characterized by a Tyr-Gly-Asp-(Thr)-Asp core flanked by hydrophobic spans five residues in length. An mRNA maturase segment is also suggested to display the motif pattern. The aspartates may be important in polymerase function by acting directly in catalysis and/or by binding magnesium.
Citations
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Journal ArticleDOI
26 Jun 1992-Science
TL;DR: A 3.5 angstrom resolution electron density map of the HIV-1 reverse transcriptase heterodimer complexed with nevirapine, a drug with potential for treatment of AIDS, reveals an asymmetric dimer.
Abstract: A 3.5 angstrom resolution electron density map of the HIV-1 reverse transcriptase heterodimer complexed with nevirapine, a drug with potential for treatment of AIDS, reveals an asymmetric dimer. The polymerase (pol) domain of the 66-kilodalton subunit has a large cleft analogous to that of the Klenow fragment of Escherichia coli DNA polymerase I. However, the 51-kilodalton subunit of identical sequence has no such cleft because the four subdomains of the pol domain occupy completely different relative positions. Two of the four pol subdomains appear to be structurally related to subdomains of the Klenow fragment, including one containing the catalytic site. The subdomain that appears likely to bind the template strand at the pol active site has a different structure in the two polymerases. Duplex A-form RNA-DNA hybrid can be model-built into the cleft that runs between the ribonuclease H and pol active sites. Nevirapine is almost completely buried in a pocket near but not overlapping with the pol active site. Residues whose mutation results in drug resistance have been approximately located.

1,902 citations

Journal ArticleDOI
TL;DR: The sequence similarity of these RNA polymerases to RT suggests that these two enzymes evolved from a common ancestor, and thus RNA polymerase can be used as an outgroup to root the RT tree.
Abstract: To study the evolutionary relationship of reverse transcriptase (RT) containing genetic elements, a phylogenetic tree of 82 retroelements from animals, plants, protozoans and bacteria was constructed. The tree was based on seven amino acid domains totalling 178 residues identified in all RTs. We have also identified these seven domains in the RNA-directed RNA polymerases from various plus-strand RNA viruses. The sequence similarity of these RNA polymerases to RT suggests that these two enzymes evolved from a common ancestor, and thus RNA polymerase can be used as an outgroup to root the RT tree. A comparison of the genetic organization of the various RT containing elements and their position on the tree allows several inferences concerning the origin and evolution of these elements. The most probable ancestor of current retroelements was a retrotransposable element with both gag-like and pol-like genes. On one major branch of the tree, organelle and bacterial sequences (e.g. group II introns and bacterial msDNA) appear to have captured the RT sequences from retrotransposons which lack long terminal repeats (LTRs). On the other major branch, acquisition of LTRs gave rise to two distinct groups of LTR retrotransposons and three groups of viruses: retroviruses, hepadnaviruses and caulimoviruses.

1,302 citations

Journal ArticleDOI
TL;DR: At the evolutionary level, the sequence similarities, gap distribution and distances between each motif strongly suggest that the ancestral polymerase module was encoded by an individual genetic element which was most closely related to the plus‐strand RNA viruses and the non‐viral retroposons.
Abstract: Four consensus sequences are conserved with the same linear arrangement in RNA-dependent DNA polymerases encoded by retroid elements and in RNA-dependent RNA polymerases encoded by plus-, minus- and double-strand RNA viruses. One of these motifs corresponds to the YGDD span previously described by Kamer and Argos (1984). These consensus sequences altogether lead to 4 strictly and 18 conservatively maintained amino acids embedded in a large domain of 120 to 210 amino acids. As judged from secondary structure predictions, each of the 4 motifs, which may cooperate to form a well-ordered domain, places one invariant amino acid in or proximal to turn structures that may be crucial for their correct positioning in a catalytic process. We suggest that this domain may constitute a prerequisite 'polymerase module' implicated in template seating and polymerase activity. At the evolutionary level, the sequence similarities, gap distribution and distances between each motif strongly suggest that the ancestral polymerase module was encoded by an individual genetic element which was most closely related to the plus-strand RNA viruses and the non-viral retroposons. This polymerase module gene may have subsequently propagated in the viral kingdom by distinct gene set recombination events leading to the wide viral variety observed today.

1,205 citations

Book
01 Dec 2018
TL;DR: This chapter presents a comprehensive review of the more recent developments in CMV biology and biochemistry that can be used as a reference work for general virologists and plant pathologists, as well as those specializing in the molecular biology of CMV and/or other multicomponent plant viruses.
Abstract: Publisher Summary Cucumber mosaic virus (CMV), the type member of the cucumovirus group, was first reported in 1916 as the causal agent of a disease of cucumber and muskmelon in Michigan and cucumber in New York. Since then, CMV has been found in most countries of the world, predominantly in the temperate zones, but increasingly more often in the tropical countries. CMV has the largest host range of any virus. The number of plant species identified as hosts for CMV has increased steadily over the past 60 years. The highlights of the more recent research include the following: (1) the complete nucleotide sequence of the genome of three strains of CMV has been determined, as well as nucleotide sequences of individual RNAs of eight other CMV strains, (2) the CMV replicase has been purified to homogeneity, and it functions in vitro to synthesize CMV RNA de novo , (3) infectious transcripts have been synthesized from full-length cDNA clones of the three strains of CMV, (4) these biologically active cDNAs are being used to map sequences involved in replication, movement, pathogenesis, resistance, and vector transmission. Biologically active cDNA clones of the satellite RNAs of CMV have been produced in seven laboratories and sequences involved in replication and pathogenicity have/are being identified, (5) finally, transgenic plants have been produced expressing either the CMV coat protein gene or satellite RNA sequences that show to protect such plants from infection by CMV. This chapter, while focusing on the more recent developments in CMV biology and biochemistry, also covers some of the same ground albeit in brief. The chapter presents a comprehensive review that can be used as a reference work for general virologists and plant pathologists, as well as those specializing in the molecular biology of CMV and/or other multicomponent plant viruses.

924 citations

Journal ArticleDOI
TL;DR: Comparative analysis of deduced amino acid sequences disclosed highly conserved regions in PB1 proteins, which may be key structures required for PB1 activities.
Abstract: We determined the origin and evolutionary pathways of the PB1 genes of influenza A viruses responsible for the 1957 and 1968 human pandemics and obtained information on the variable or conserved region of the PB1 protein. The evolutionary tree constructed from nucleotide sequences suggested the following: (i) the PB1 gene of the 1957 human pandemic strain, A/Singapore/1/57 (H2N2), was probably introduced from avian species and was maintained in humans until 1968; (ii) in the 1968 pandemic strain, A/NT/60/68 (H3N2), the PB1 gene was not derived from the previously circulating virus in humans but probably from another avian virus; and (iii) a current human H3N2 virus inherited the PB1 gene from an A/NT/60/68-like virus. Nucleotide sequence analysis also showed that the avian PB1 gene was introduced into pigs. Hence, transmission of the PB1 gene from avian to mammalian species is a relatively frequent event. Comparative analysis of deduced amino acid sequences disclosed highly conserved regions in PB1 proteins, which may be key structures required for PB1 activities.

779 citations


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