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All the three domains are required for the two known integration reactions. CCD contains the catalytic triad and is believed to bind viral DNA specifically, and CTD binds viral DNA in a nonspecific manner. As no clear evidence has confirmed the involvement of NTD in DNA binding directly, NTD has not been seriously considered and less is known about its function in viral replication. In the current work, using a SPR technology\u2010based assay, the HIV\u20101 viral DNA was determined to bind directly to NTD with a <jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub> value of 8.8\u2005\u03bc<jats:sc>M<\/jats:sc>, suggesting that the process of preintegrated complex formation for HIV\u20101 IN might involve the direct interaction of NTD with viral DNA in addition to binding of viral DNA to the catalytic core domain and C\u2010terminal domain. Moreover, such viral DNA\/IN binding could be inhibited by the marine product hyrtiosal from the marine sponge <jats:italic>Hyrtios erectus<\/jats:italic> with an IC<jats:sub>50<\/jats:sub> of 9.60\u00b10.86\u2005\u03bc<jats:sc>M<\/jats:sc>. Molecular dynamic analysis correlated with a site\u2010directed mutagenesis approach further revealed that such hyrtiosal\u2010induced viral DNA\/IN binding inhibition was caused by the fact that hyrtiosal could bind HIV\u20101 NTD at Ser17, Trp19, and Lys34. As hyrtiosal was recently discovered by us as a protein tyrosine phosphatase 1B (PTP1B) inhibitor, this work might also supply multiple\u2010target information for this marine product, and the verified HIV\u2010NTD\/HIV\u20101 IN interaction model could have further implications for new HIV\u20101 IN inhibitor design and evaluation.<\/jats:p>","DOI":"10.1002\/cmdc.200700223","type":"journal-article","created":{"date-parts":[[2007,10,17]],"date-time":"2007-10-17T09:51:35Z","timestamp":1192614695000},"page":"173-180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Hyrtiosal, from the Marine Sponge <i>Hyrtios erectus<\/i>, Inhibits HIV\u20101 Integrase Binding to Viral DNA by a New Inhibitor Binding Site"],"prefix":"10.1002","volume":"3","author":[{"given":"Li","family":"Du","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuewei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hualiang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,1,3]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200600349"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5322.112"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1995.1148"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026043388448"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-3542(00)00083-8"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026043388547"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3527(08)60307-3"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1660"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209278200"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.13659"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0797-567"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.7333"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026043388394"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.2174\/157489106775244082"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.20054"},{"key":"e_1_2_7_16_2","unstructured":"Merck http:\/\/www.hivdent.org\/drugs1\/drugMMCP0206.htm2006."},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60597-2"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2006.11.080"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511254103"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.030817"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi960541u"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001436200"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.41.25809"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105072200"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2001.01932.x"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi000397j"},{"key":"e_1_2_7_27_2","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1093\/nar\/gki241","volume":"33","author":"Faure A.","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.150220297"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi982870n"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005499200"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.19.12584-12591.2005"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/np000115g"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.13.7712"},{"key":"e_1_2_7_35_2","unstructured":"SYBYL. 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