https://scholars.lib.ntu.edu.tw/handle/123456789/416772
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Huang, Chang-Yu | en_US |
dc.contributor.author | YEE-CHUN CHEN | en_US |
dc.contributor.author | Wu-Hsieh, Betty A | en_US |
dc.contributor.author | Fang, J.-M. | en_US |
dc.contributor.author | ZEE-FEN CHANG | en_US |
dc.creator | Huang, Chang-Yu;Yee-Chun Chen;Wu-Hsieh, Betty A;Jim-Min Fang;Zee-Fen Chang | - |
dc.date.accessioned | 2019-08-29T03:17:04Z | - |
dc.date.available | 2019-08-29T03:17:04Z | - |
dc.date.issued | 2019-07-05 | - |
dc.identifier.issn | 00219258 | - |
dc.identifier.uri | 10.1074/jbc.RA118.006798 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/416772 | - |
dc.description.abstract | The yeast Candida albicans is the most prevalent opportunistic fungal pathogen in humans. Drug resistance among C. albicans isolates poses a common challenge, and overcoming this resistance represents an unmet need in managing this common pathogen. Here, we investigated CDC8, encoding thymidylate kinase (TMPK), as a potential drug target for the management of C. albicans infections. We found that the region spanning amino acids 106-123, namely the Ca-loop of C. albicans TMPK (CaTMPK), contributes to the hyperactivity of this enzyme compared with the human enzyme (hTMPK) and to the utilization of deoxyuridine monophosphate (dUMP)/deoxy-5-fluorouridine monophosphate (5-FdUMP) as a substrate. Notably, expression of CaTMPK, but not of hTMPK, produced dUTP/5-FdUTP-mediated DNA toxicity in budding yeast (Saccharomyces cerevisiae). CRISPR-mediated deletion of this Ca-loop in C. albicans revealed that the Ca-loop is critical for fungal growth and susceptibility to 5-fluorouridine (5-FUrd). Of note, pathogenic and drug-resistant C. albicans clones were similarly sensitive to 5-FUrd, and we also found that CaTMPK is essential for the growth of C. albicans In conclusion, these findings not only identified a target site for the development of CaTMPK-selective drugs, but also revealed that 5-FUrd may have potential utility as drug for managing C. albicans infections. | en_US |
dc.language.iso | en | en_US |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | en_US |
dc.relation.ispartof | The Journal of biological chemistry | en_US |
dc.subject | Candida albicans; DNA damage; drug resistance; nucleoside/nucleotide analogue; substrate specificity; thymidylate kinase | en_US |
dc.title | The Ca-loop in thymidylate kinase is critical for growth and contributes to pyrimidine drug sensitivity of Candida albicans | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1074/jbc.RA118.006798 | - |
dc.identifier.pmid | 31152062 | - |
dc.identifier.scopus | 2-s2.0-85069036569 | - |
dc.identifier.isi | WOS:000478717100026 | - |
dc.identifier.url | https://api.elsevier.com/content/abstract/scopus_id/85069036569 | - |
dc.relation.pages | 10686 | en_US |
dc.relation.journalvolume | 294 | en_US |
dc.relation.journalissue | 27 | en_US |
dc.relation.pageend | 10697 | en_US |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.languageiso639-1 | en | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
crisitem.author.dept | Internal Medicine | - |
crisitem.author.dept | Internal Medicine-NTUH | - |
crisitem.author.dept | Center for Infection Control | - |
crisitem.author.dept | Chemistry | - |
crisitem.author.dept | Molecular Medicine | - |
crisitem.author.orcid | 0000-0002-1816-9010 | - |
crisitem.author.orcid | 0000-0002-6070-3408 | - |
crisitem.author.orcid | 0000-0003-3011-284X | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Science | - |
crisitem.author.parentorg | College of Medicine | - |
Appears in Collections: | 分子醫學研究所 |
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