{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:06:20Z","timestamp":1787166380716,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,2,5]],"date-time":"2022-02-05T00:00:00Z","timestamp":1644019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The Kaposi's sarcoma\u2010associated herpesvirus protease is essential for virus maturation. This protease functions under allosteric regulation that establishes its enzymatic activity upon dimerization. It exists in equilibrium between an inactive monomeric state and an active, weakly associating, dimeric state that is stabilized upon ligand binding. The dynamics of the protease dimer and its monomer were studied using the Gaussian network model and the anisotropic network model , and its role in mediating the allosteric regulation is demonstrated. We show that the dimer is composed of five dynamical domains. The central domain is formed upon dimerization and composed of helix five of each monomer, in addition to proximal and distal domains of each monomer. Dimerization reduces the mobility of the central domains and increases the mobility of the distal domains, in particular the binding site within them. The three slowest ANM modes of the dimer assist the protease in ligand binding, motion of the conserved Arg142 and Arg143 toward the oxyanion, and reducing the activation barrier for the tetrahedral transition state by stretching the bond that is cleaved by the protease. In addition, we show that ligand binding reduces the motion of helices \u03b11 and \u03b15 at the interface and explain how ligand binding can stabilize the dimer.<\/jats:p>","DOI":"10.1002\/prot.26307","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T05:14:12Z","timestamp":1643260452000},"page":"1267-1277","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The effect of dimerization and ligand binding on the dynamics of Kaposi's sarcoma\u2010associated herpesvirus protease"],"prefix":"10.1002","volume":"90","author":[{"given":"David","family":"Bern","sequence":"first","affiliation":[{"name":"Department of Molecular Biology Ariel University  Ariel Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-2751","authenticated-orcid":false,"given":"Dror","family":"Tobi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Ariel University  Ariel Israel"},{"name":"Department of Computer Sciences Ariel University  Ariel Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi5003234"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2888"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0060-9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1065"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi001019h"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.9.7030-7038.1997"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.000872"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.07.073"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2791"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(99)80023-2"},{"key":"e_1_2_7_12_1","volume-title":"Normal Mode Analysis. 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