{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T22:52:35Z","timestamp":1772059955657,"version":"3.50.1"},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,8,5]],"date-time":"2003-08-05T00:00:00Z","timestamp":1060041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2003,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\u03b2\u2010Lactam antibiotics inhibit enzymes involved in the last step of peptidoglycan synthesis. These enzymes, also identified as penicillin\u2010binding proteins (PBPs), form a long\u2010lived acyl\u2010enzyme complex with \u03b2\u2010lactams. Antibiotic resistance is mainly due to the production of \u03b2\u2010lactamases, which are enzymes that hydrolyze the antibiotics and so prevent them reaching and inactivating their targets, and to mutations of the PBPs that decrease their affinity for the antibiotics. In this study, we present a theoretical study of several penicillin\u2010recognizing proteins complexed with various \u03b2\u2010lactam antibiotics. Hybrid quantum mechanical\/molecular mechanical potentials in conjunction with molecular dynamics simulations have been performed to understand the role of several residues, and pK<jats:sub>a<\/jats:sub> calculations have also been done to determine their protonation state. We analyze the differences between the \u03b2\u2010lactamase TEM\u20101, the membrane\u2010bound PBP2x of <jats:italic>Streptococcus pneumoniae<\/jats:italic>, and the soluble DD\u2010transpeptidase of <jats:italic>Streptomyces K15<\/jats:italic>. Proteins 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.10450","type":"journal-article","created":{"date-parts":[[2003,8,25]],"date-time":"2003-08-25T13:14:30Z","timestamp":1061817270000},"page":"88-100","source":"Crossref","is-referenced-by-count":32,"title":["Understanding the acylation mechanisms of active\u2010site serine penicillin\u2010recognizing proteins: A molecular dynamics simulation study"],"prefix":"10.1002","volume":"53","author":[{"given":"M\u00f3nica","family":"Oliva","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Otto","family":"Dideberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin J.","family":"Field","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,8,5]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.54.1.75"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.54.4.1133"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.257.5073.1064"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/35021219"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3107125"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2450911"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1993.tb05954.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1128\/AAC.40.4.829","article-title":"Penicillin\u2010binding proteins 2b and 2x of Streptococcus pneumoniae are primary resistance determinants for different classes of \u03b2\u2010lactam antibiotics","volume":"40","author":"Grebe T","year":"1996","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0396-284"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.3740"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/359700a0"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340160406"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi990758z"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2790213"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(01)00194-0"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10058"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4838(94)00177-I"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3300581"},{"key":"e_1_2_6_20_2","doi-asserted-by":"crossref","first-page":"3186","DOI":"10.1016\/S0021-9258(18)49972-3","article-title":"Site\u2010directed mutants, at position 166, of RTEM\u20101 \u03b2\u2010lactamase that form a stable acyl\u2010enzyme intermediate with penicillin","volume":"266","author":"Adachi H","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.9.5438"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0259640"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.10129"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2002.02815.x"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2720613"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.8.2.404"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.5.1747"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(00)00534-7"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.241442898"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1039\/a908264f"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja017156z"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm9506027"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp012881h"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-461X(1999)73:2<161::AID-QUA10>3.0.CO;2-E"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1139\/v94-131"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.060027897"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444902003451"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja9609718"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.31.21853"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1301"},{"key":"e_1_2_6_41_2","unstructured":"DavidL.Mod\u00e9lisation des interactions \u00e9lectrostatiques des biomolo\u00e9cules en solution. 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