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To block the antimicrobial activity of these antibiotics, bacteria have evolved lactamases that render them inert. Among these, TEM\u20101, a class A lactamase, has been extensively studied. In 2004, Horn et al. described a novel allosteric TEM\u20101 inhibitor, FTA, that binds distant from the TEM\u20101 orthosteric (penicillin\u2010binding) pocket. TEM\u20101 has subsequently become a model for the study of allostery. In the present work, we perform molecular dynamics simulations of FTA\u2010bound and FTA\u2010absent TEM\u20101, totaling ~3\u00a0\u03bcS, that provide new insight into TEM\u20101 inhibition. In one of the simulations, bound FTA assumed a conformation different than that observed crystallographically. We provide evidence that the alternate pose is physiologically plausible and describe how it impacts our understanding of TEM\u20101 allostery.<\/jats:p>","DOI":"10.1002\/pro.4622","type":"journal-article","created":{"date-parts":[[2023,3,12]],"date-time":"2023-03-12T07:54:36Z","timestamp":1678607676000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Allosteric inhibition of <scp>TEM<\/scp>\u20101 \u03b2 lactamase: Microsecond molecular dynamics simulations provide mechanistic insights"],"prefix":"10.1002","volume":"32","author":[{"given":"Erich","family":"Hellemann","sequence":"first","affiliation":[{"name":"Department of Biological Sciences University of Pittsburgh  Pittsburgh Pennsylvania 15260 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amrita","family":"Nallathambi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Pittsburgh  Pittsburgh 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