Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 3.9 kb DNA fragment containing the dnaA gene region of Mycobacterium avium was cloned and its nucleotide sequence was determined. Nucleotide sequence analyses indicated that this region encodes three genes in the order rpmH (ribosomal protein L34), dnaA (the putative initiator protein) and dnaN (the beta subunit of DNA polymerase III). The intergenic regions between the rpmH-dnaA and dnaA-dnaN genes were found to contain several putative DnaA boxes, 9 nt long DnaA protein recognition sequences. A DNA fragment containing the 3' but not the 5' flanking region of the M. avium dnaA gene when cloned in Escherichia coli plasmids, which are otherwise non-replicative in mycobacteria, exhibited autonomous replication activity in M. avium but not in Mycobacterium bovis BCG and Mycobacterium smegmatis. The 5' flanking region of dnaA, on the other hand, exhibited autonomous replication activity in M. bovis BCG but not in M. avium and M. smegmatis. The implications of these results for the understanding of the M. avium oriC replication initiation process are discussed.
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PMID:The dnaA gene region of Mycobacterium avium and the autonomous replication activities of its 5' and 3' flanking regions. 1053 13

The in vivo induced antigen technology (IVIAT)(1) has been used for the identification of open reading frames (ORFs) which could be possible therapeutic targets. A recombinant lambdagt11:: Mycobacterium tuberculosis H37Rv expression library was screened with pooled TB patient sera preabsorbed with in vitro grown M. tuberculosis H37Rv. Preabsorption of pooled TB patient sera allowed identification of antigens specifically expressed or upregulated during infection and growth in vivo. Six ORFs were identified, of which four (rv0287, rv2402, rv3878 and rv1045) were of hypothetical functions. Rv0287 is a probable regulatory protein. Rv3878 is present uniquely in M. tuberculosis H37Rv and is a part of RDI deletion region of M. bovis BCG, which includes esat 6 region. This could be exploited as a tool for diagnosis. Two ORFs were assigned function solely on the basis of homology, dnaQ (rv3711c) and lpdA (rv3303c). dnaQ codes for the epsilon subunit of DNA polymerase III, which is responsible for the proofreading activity of the complex. lpdA codes for dihydrolipoamide dehydrogenase, which is a part of many multienzyme complexes such as pyruvate dehydrogenase, keto-acid dehydrogenase and alpha-ketoglutarate dehydrogenase. These two enzymes appear to be potential targets for drug development.
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PMID:Selective identification of new therapeutic targets of Mycobacterium tuberculosis by IVIAT approach. 1246 89

One 2-year-old undernourished girl presented to our outpatient with large erythematous scaly plaques in arm along with multiple bony swellings over nose, fingers, left foot, and back for the past 1 year. Apart from skin and bone lesions the girl was also had intermittent fever, pallor, irritability, and malnourishment. Her parents gave a history of incomplete healing at the BCG vaccination site. The case was diagnosed to be case of disseminated mycobacterial infection skin and bone with the help of histopathology, radiological examination, and DNA polymerase chain reaction (PCR). DNA PCR from the skin lesion came positive for mycobacteria tuberculosis complex. The girl was treated with 6 months of standard antitubercular drug treatment with very good improvement not only of her cutaneous and bone changes but also of her general health and growth. We report the case because paucity of similar infection in literature and for greater recognition of potential epidemiological threat.
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PMID:BCG-induced Disseminated Mycobacterial Infection of Skin and Bone in an Otherwise Immunocompetent Child. 2897 17