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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Investigations into microsporidian methionine aminopeptidase type 2: a therapeutic target for microsporidiosis</title><author><name sortKey="Zhang, Hong" sort="Zhang, Hong" uniqKey="Zhang H" first="Hong" last="Zhang">Hong Zhang</name><affiliation><nlm:aff id="A1">Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA</nlm:aff></affiliation></author><author><name sortKey="Huang, Huan" sort="Huang, Huan" uniqKey="Huang H" first="Huan" last="Huang">Huan Huang</name><affiliation><nlm:aff id="A1">Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA</nlm:aff></affiliation></author><author><name sortKey="Cali, Ann" sort="Cali, Ann" uniqKey="Cali A" first="Ann" last="Cali">Ann Cali</name><affiliation><nlm:aff id="A2">Department of Biologic Sciences, Rutgers University, Newark, New Jersey 07102, USA</nlm:aff></affiliation></author><author><name sortKey="Takvorian, Peter M" sort="Takvorian, Peter M" uniqKey="Takvorian P" first="Peter M." last="Takvorian">Peter M. Takvorian</name><affiliation><nlm:aff id="A2">Department of Biologic Sciences, Rutgers University, Newark, New Jersey 07102, USA</nlm:aff></affiliation></author><author><name sortKey="Feng, Xiaochuan" sort="Feng, Xiaochuan" uniqKey="Feng X" first="Xiaochuan" last="Feng">Xiaochuan Feng</name><affiliation><nlm:aff id="A3">Division of Infectious Diseases, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts 01536, USA</nlm:aff></affiliation></author><author><name sortKey="Zhou, Ghou" sort="Zhou, Ghou" uniqKey="Zhou G" first="Ghou" last="Zhou">Ghou Zhou</name><affiliation><nlm:aff id="A4">Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA</nlm:aff></affiliation></author><author><name sortKey="Weiss, Louis M" sort="Weiss, Louis M" uniqKey="Weiss L" first="Louis M." last="Weiss">Louis M. Weiss</name><affiliation><nlm:aff id="A1">Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">16004378</idno><idno type="pmc">3109671</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109671</idno><idno type="RBID">PMC:3109671</idno><date when="2005">2005</date><idno type="wicri:Area/Pmc/Corpus">000290</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000290</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Investigations into microsporidian methionine aminopeptidase type 2: a therapeutic target for microsporidiosis</title><author><name sortKey="Zhang, Hong" sort="Zhang, Hong" uniqKey="Zhang H" first="Hong" last="Zhang">Hong Zhang</name><affiliation><nlm:aff id="A1">Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA</nlm:aff></affiliation></author><author><name sortKey="Huang, Huan" sort="Huang, Huan" uniqKey="Huang H" first="Huan" last="Huang">Huan Huang</name><affiliation><nlm:aff id="A1">Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA</nlm:aff></affiliation></author><author><name sortKey="Cali, Ann" sort="Cali, Ann" uniqKey="Cali A" first="Ann" last="Cali">Ann Cali</name><affiliation><nlm:aff id="A2">Department of Biologic Sciences, Rutgers University, Newark, New Jersey 07102, USA</nlm:aff></affiliation></author><author><name sortKey="Takvorian, Peter M" sort="Takvorian, Peter M" uniqKey="Takvorian P" first="Peter M." last="Takvorian">Peter M. Takvorian</name><affiliation><nlm:aff id="A2">Department of Biologic Sciences, Rutgers University, Newark, New Jersey 07102, USA</nlm:aff></affiliation></author><author><name sortKey="Feng, Xiaochuan" sort="Feng, Xiaochuan" uniqKey="Feng X" first="Xiaochuan" last="Feng">Xiaochuan Feng</name><affiliation><nlm:aff id="A3">Division of Infectious Diseases, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts 01536, USA</nlm:aff></affiliation></author><author><name sortKey="Zhou, Ghou" sort="Zhou, Ghou" uniqKey="Zhou G" first="Ghou" last="Zhou">Ghou Zhou</name><affiliation><nlm:aff id="A4">Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA</nlm:aff></affiliation></author><author><name sortKey="Weiss, Louis M" sort="Weiss, Louis M" uniqKey="Weiss L" first="Louis M." last="Weiss">Louis M. Weiss</name><affiliation><nlm:aff id="A1">Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Folia parasitologica</title><idno type="ISSN">0015-5683</idno><imprint><date when="2005">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">The Microsporidia have been reported to cause a wide range of clinical diseases particularly in patients that are immunosuppressed. They can infect virtually any organ system and cases of gastrointestinal infection, encephalitis, ocular infection, sinusitis, myositis and disseminated infection are well described in the literature. While benzimidazoles such as albendazole are active against many species of Microsporidia, these drugs do not have significant activity against <italic>Enterocytozoon bieneusi</italic>. Fumagillin, ovalicin and their analogues have been demonstrated to have antimicrosporidial activity <italic>in vitro</italic> and in animal models of microsporidiosis. Fumagillin has also been demonstrated to have efficacy in human infections due to <italic>E. bieneusi</italic>. Fumagillin is an irreversible inhibitor of methionine aminopeptidase type 2 (MetAP2). Homology cloning employing the polymerase chain reaction was used to identify the MetAP2 gene from the human pathogenic microsporidia Encephalitozoon cuniculi, Encephalitozoon hellem, Encephalitozoon intestinalis, Brachiola algerae and <italic>E. bieneusi</italic>. The full-length MetAP2 coding sequence was obtained for all of the Encephalitozoonidae. Recombinant <italic>E. cuniculi</italic> MetAP2 was produced in baculovirus and purified using chromatographic techniques. The <italic>in vitro</italic> activity and effect of the inhibitors bestatin and TNP-470 on this recombinant microsporidian MetAP2 was characterized. An <italic>in silico</italic> model of <italic>E. cuniculi</italic> MetAP2 was developed based on crystallographic data on human MetAP2. These reagents provide new tools for the development of <italic>in vitro</italic> assay systems to screen candidate compounds for use as new therapeutic agents for the treatment of microsporidiosis.</p></div></front></TEI><pmc article-type="research-article" xml:lang="en"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0065750</journal-id><journal-id journal-id-type="pubmed-jr-id">3750</journal-id><journal-id journal-id-type="nlm-ta">Folia Parasitol (Praha)</journal-id><journal-title-group><journal-title>Folia parasitologica</journal-title></journal-title-group><issn pub-type="ppub">0015-5683</issn></journal-meta><article-meta><article-id pub-id-type="pmid">16004378</article-id><article-id pub-id-type="pmc">3109671</article-id><article-id pub-id-type="manuscript">NIHMS287894</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Investigations into microsporidian methionine aminopeptidase type 2: a therapeutic target for microsporidiosis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Hong</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Huang</surname><given-names>Huan</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Cali</surname><given-names>Ann</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Takvorian</surname><given-names>Peter M.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Feng</surname><given-names>Xiaochuan</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Zhou</surname><given-names>Ghou</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Weiss</surname><given-names>Louis M.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A5">5</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA</aff><aff id="A2"><label>2</label>Department of Biologic Sciences, Rutgers University, Newark, New Jersey 07102, USA</aff><aff id="A3"><label>3</label>Division of Infectious Diseases, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts 01536, USA</aff><aff id="A4"><label>4</label>Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA</aff><aff id="A5"><label>5</label>Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA</aff><author-notes><corresp id="CR1">Address for correspondence: L.M. Weiss, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Room 504, Forchheimer Building, Bronx, NY 10461, USA. Phone: ++1 718 430 2142; Fax: ++1 718 430 8543; <email>lmweiss@aecom.yu.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>13</day><month>4</month><year>2011</year></pub-date><pub-date pub-type="ppub"><month>5</month><year>2005</year></pub-date><pub-date pub-type="pmc-release"><day>7</day><month>6</month><year>2011</year></pub-date><volume>52</volume><issue>1-2</issue><fpage>182</fpage><lpage>192</lpage><abstract><p id="P1">The Microsporidia have been reported to cause a wide range of clinical diseases particularly in patients that are immunosuppressed. They can infect virtually any organ system and cases of gastrointestinal infection, encephalitis, ocular infection, sinusitis, myositis and disseminated infection are well described in the literature. While benzimidazoles such as albendazole are active against many species of Microsporidia, these drugs do not have significant activity against <italic>Enterocytozoon bieneusi</italic>. Fumagillin, ovalicin and their analogues have been demonstrated to have antimicrosporidial activity <italic>in vitro</italic> and in animal models of microsporidiosis. Fumagillin has also been demonstrated to have efficacy in human infections due to <italic>E. bieneusi</italic>. Fumagillin is an irreversible inhibitor of methionine aminopeptidase type 2 (MetAP2). Homology cloning employing the polymerase chain reaction was used to identify the MetAP2 gene from the human pathogenic microsporidia Encephalitozoon cuniculi, Encephalitozoon hellem, Encephalitozoon intestinalis, Brachiola algerae and <italic>E. bieneusi</italic>. The full-length MetAP2 coding sequence was obtained for all of the Encephalitozoonidae. Recombinant <italic>E. cuniculi</italic> MetAP2 was produced in baculovirus and purified using chromatographic techniques. The <italic>in vitro</italic> activity and effect of the inhibitors bestatin and TNP-470 on this recombinant microsporidian MetAP2 was characterized. An <italic>in silico</italic> model of <italic>E. cuniculi</italic> MetAP2 was developed based on crystallographic data on human MetAP2. These reagents provide new tools for the development of <italic>in vitro</italic> assay systems to screen candidate compounds for use as new therapeutic agents for the treatment of microsporidiosis.</p></abstract><kwd-group><kwd>Microsporidia</kwd><kwd>methionine aminopeptidase type 2</kwd><kwd>MetAP2</kwd><kwd><italic>Enterocytozoon</italic></kwd><kwd><italic>Encephalitozoon</italic></kwd><kwd><italic>Brachiola</italic></kwd><kwd>therapeutics</kwd></kwd-group><funding-group><award-group><funding-source country="United States">National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID</funding-source><award-id>R21 AI069953-02 || AI</award-id></award-group><award-group><funding-source country="United States">National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID</funding-source><award-id>R21 AI052035-02 || AI</award-id></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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