{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T01:16:53Z","timestamp":1769044613237,"version":"3.49.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"15","license":[{"start":{"date-parts":[[2016,11,10]],"date-time":"2016-11-10T00:00:00Z","timestamp":1478736000000},"content-version":"vor","delay-in-days":826,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Considering that all natural nucleotides (D-dNTPs) and the building blocks (D-dNMPs) of DNA chains possess D-stereochemistry, DNA polymerases and reverse transcriptases (RTs) likely possess strongD-stereoselectivity by preferably binding and incorporating D-dNTPs over unnatural L-dNTPs during DNA synthesis. Surprisingly, a structural basis for the discrimination against L-dNTPs by DNA polymerases or RTs has not been established although L-deoxycytidine analogs (lamivudine and emtricitabine) and L-thymidine (telbivudine) have been widely used as antiviral drugs for years. Here we report seven high-resolution ternary crystal structures of a prototype Y-family DNA polymerase, DNA, and D-dCTP, D-dCDP, L-dCDP, or the diphosphates and triphosphates of lamivudine and emtricitabine. These structures reveal that relative to D-dCTP, each of these L-nucleotides has its sugar ring rotated by 180\u00b0 with an unusual O4\u2032-endo sugar puckering and exhibits multiple triphosphate-binding conformations within the active site of the polymerase. Such rare binding modes significantly decrease the incorporation rates and efficiencies of these L-nucleotides catalyzed by the polymerase.<\/jats:p>","DOI":"10.1093\/nar\/gku709","type":"journal-article","created":{"date-parts":[[2014,8,8]],"date-time":"2014-08-08T04:33:36Z","timestamp":1407472416000},"page":"9984-9995","source":"Crossref","is-referenced-by-count":24,"title":["Structural and kinetic insights into binding and incorporation of L-nucleotide analogs by a Y-family DNA polymerase"],"prefix":"10.1093","volume":"42","author":[{"given":"Vineet","family":"Gaur","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajan","family":"Vyas","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason D.","family":"Fowler","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia","family":"Efthimiopoulos","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joy Y.","family":"Feng","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94044, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zucai","family":"Suo","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,8,7]]},"reference":[{"key":"2019070601434938600_B1","doi-asserted-by":"crossref","first-page":"14411","DOI":"10.1074\/jbc.M705006200","article-title":"Base pair hydrogen bonds are essential for proofreading selectivity by the human mitochondrial DNA polymerase","volume":"283","author":"Lee","year":"2008","journal-title":"J. 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