{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T16:57:15Z","timestamp":1769965035945,"version":"3.49.0"},"reference-count":72,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2002,10,17]],"date-time":"2002-10-17T00:00:00Z","timestamp":1034812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Comput Chem"],"published-print":{"date-parts":[[2002,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The acylation step of the catalytic mechanism of \u03b2\u2010lactamases and penicillin\u2010binding proteins (PBPs) has been studied with various approaches. The methods applied range from molecular dynamics (MD) simulations to multiple titration calculations using the Poisson\u2013Boltzmann approach to quantum mechanical (QM) methods. The mechanism of class A \u03b2\u2010lactamases was investigated in the greatest detail. Most approaches support the critical role of Glu\u2010166 and hydrolytic water in the acylation step of the enzymatic catalysis in class A \u03b2\u2010lactamases. The details of the catalytic mechanism have been revealed by the QM approach, which clearly pointed out the critical role of Glu\u2010166 acting as a general base in the acylation step with preferred substrates. Lys\u201073 shuffles a proton abstracted by Glu\u2010166 O<jats:sub>\u03b5<\/jats:sub> to the \u03b2\u2010lactam nitrogen through Ser\u2010130 hydroxyl. This proton is transferred from O<jats:sub>\u03b3<\/jats:sub> of the catalytic Ser\u201070 through the bridging hydrolytic water to Glu\u2010166 O<jats:sub>\u03b5<\/jats:sub>. Then the hydrogen is simultaneously passed through S<jats:sub><jats:italic>N<\/jats:italic><\/jats:sub>2 inversion mechanism at Lys\u201073 N<jats:sub>\u03b6<\/jats:sub> to Ser\u2010130 O<jats:sub>\u03b3<\/jats:sub>, which loses its proton to the \u03b2\u2010lactam nitrogen. The protonation of \u03b2\u2010lactam nitrogen proceeds with an immediate ring opening and collapse of the first tetrahedral species into an acyl\u2010enzyme intermediate. However, the studies that considered the effect of solvation lower the barrier for the pathway, which utilizes Lys\u201073 as a general base, thus creating a possibility of multiple mechanisms for the acylation step in the class A \u03b2\u2010lactamases. These findings help explain the exceptional efficiency of these enzymes. They emphasize an important role of Glu\u2010166, Lys\u201073, and Ser\u2010130 for enzymatic catalysis and shed light on details of the acylation step of class A \u03b2\u2010lactamase mechanism. The acylation step for class C \u03b2\u2010lactamases and six classes of PBPs were also considered with continuum solvent models and MD simulations. \u00a9 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1559\u20131576, 2002<\/jats:p>","DOI":"10.1002\/jcc.10129","type":"journal-article","created":{"date-parts":[[2002,12,24]],"date-time":"2002-12-24T01:14:58Z","timestamp":1040692498000},"page":"1559-1576","source":"Crossref","is-referenced-by-count":28,"title":["p<i>K<\/i><sub>a<\/sub>, MM, and QM studies of mechanisms of \u03b2\u2010lactamases and penicillin\u2010binding proteins: Acylation step"],"prefix":"10.1002","volume":"23","author":[{"given":"Irina","family":"Massova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Kollman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,10,17]]},"reference":[{"issue":"1","key":"e_1_2_6_2_2","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1093\/clinids\/24.Supplement_1.S19","author":"Medeiros A. 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