{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:53:40Z","timestamp":1791053620865,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2010,6,16]],"date-time":"2010-06-16T00:00:00Z","timestamp":1276646400000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Racemization of aspartic acid residues in peptides and proteins is assumed to proceed <jats:italic>via<\/jats:italic> succinimide intermediates. An enolization of the succinimide intermediate is required for the racemization to occur. In this study, we modeled the enolization step by density\u2010functional theory (DFT) calculations (B3LYP\/6\u201031+G**), using two model compounds, <jats:italic>N<\/jats:italic>\u2010methylsuccinimide (<jats:bold>1<\/jats:bold>) and its formylamino derivarive <jats:bold>2<\/jats:bold>. Three mechanisms were investigated for <jats:bold>1<\/jats:bold>, <jats:italic>i.e.<\/jats:italic>, the direct mechanism without active participation of H<jats:sub>2<\/jats:sub>O molecules, and one\u2010H<jats:sub>2<\/jats:sub>O and two\u2010H<jats:sub>2<\/jats:sub>O mechanisms, in which one or two H<jats:sub>2<\/jats:sub>O molecules actively participate in the reaction. We found that the two\u2010H<jats:sub>2<\/jats:sub>O mechanism was the most favorable with an activation barrier of 37\u2005kcal mol<jats:sup>\u22121<\/jats:sup>. In the two\u2010H<jats:sub>2<\/jats:sub>O mechanism, a concerted bond reorganization involving a triple H\u2010atom transfer occurred in an eight\u2010membered cyclic structure formed between the imide and two H<jats:sub>2<\/jats:sub>O molecules. For <jats:bold>2<\/jats:bold>, we investigated only the two\u2010H<jats:sub>2<\/jats:sub>O mechanism and found that the activation barrier was lowered to 31\u2005kcal mol<jats:sup>\u22121<\/jats:sup> due to an H\u2010bond between the CO O\u2010atom of the formylamino group (\u2018the neighboring residue\u2019) and one of the H<jats:sub>2<\/jats:sub>O molecules. Our results suggest that, in proteins, the Asp racemization is severely controlled by the accessibility of H<jats:sub>2<\/jats:sub>O molecules to the reaction site of the succinimide intermediate.<\/jats:p>","DOI":"10.1002\/cbdv.200900296","type":"journal-article","created":{"date-parts":[[2010,6,18]],"date-time":"2010-06-18T16:45:53Z","timestamp":1276879553000},"page":"1349-1356","source":"Crossref","is-referenced-by-count":36,"title":["Modeling the Enolization of Succinimide Derivatives, a Key Step of Racemization of Aspartic Acid Residues: Importance of a Two\u2010H<sub>2<\/sub>O Mechanism"],"prefix":"10.1002","volume":"7","author":[{"given":"Ohgi","family":"Takahashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akifumi","family":"Oda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,6,16]]},"reference":[{"key":"e_1_2_1_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)75855-4"},{"key":"e_1_2_1_1_3","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)83327-0"},{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja953505b"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(01)00258-8"},{"key":"e_1_2_1_3_3","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-003-0050-8"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1988.tb13231.x"},{"key":"e_1_2_1_4_3","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)53661-9"},{"key":"e_1_2_1_4_4","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)34045-0"},{"key":"e_1_2_1_4_5","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.10.014"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0047-6374(01)00363-3"},{"key":"e_1_2_1_5_3","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.1585"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(19970115)18:1<56::AID-JCC6>3.0.CO;2-Z"},{"key":"e_1_2_1_6_3","doi-asserted-by":"publisher","DOI":"10.1021\/ja972017w"},{"key":"e_1_2_1_6_4","doi-asserted-by":"publisher","DOI":"10.1021\/jp982713y"},{"key":"e_1_2_1_6_5","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphys.2008.02.016"},{"key":"e_1_2_1_6_6","doi-asserted-by":"publisher","DOI":"10.1016\/j.theochem.2008.08.004"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi052438n"},{"key":"e_1_2_1_7_3","doi-asserted-by":"publisher","DOI":"10.1021\/jp056991q"},{"key":"e_1_2_1_7_4","doi-asserted-by":"publisher","DOI":"10.1021\/jp8015497"},{"key":"e_1_2_1_7_5","doi-asserted-by":"publisher","DOI":"10.1021\/jp808597v"},{"key":"e_1_2_1_8_2","unstructured":"Spartan'04 Wavefunction Inc. 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