{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T20:29:20Z","timestamp":1780950560327,"version":"3.54.1"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2015,4,7]],"date-time":"2015-04-07T00:00:00Z","timestamp":1428364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1004061","type":"journal-article","created":{"date-parts":[[2015,4,7]],"date-time":"2015-04-07T14:28:39Z","timestamp":1428416919000},"page":"e1004061","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["Stepwise Catalytic Mechanism via Short-Lived Intermediate Inferred from Combined QM\/MM MERP and PES Calculations on Retaining Glycosyltransferase ppGalNAcT2"],"prefix":"10.1371","volume":"11","author":[{"given":"Tom\u00e1\u0161","family":"Trnka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav","family":"Kozmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Tvaro\u0161ka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslav","family":"Ko\u010da","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,4,7]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s000180050146","article-title":"Enzyme action in glycoprotein synthesis","volume":"54","author":"P Sears","year":"1998","journal-title":"Cell Mol Life Sci"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1007\/s00018-007-6551-y","article-title":"Modulation of protein biophysical properties by chemical glycosylation: biochemical insights and biomedical implications","volume":"64","author":"RJ Sol\u00e1","year":"2007","journal-title":"Cell Mol Life Sci"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.tibtech.2004.07.012","article-title":"Sugar-mediated ligand\u2013receptor interactions in the immune system","volume":"22","author":"PM Rudd","year":"2004","journal-title":"Trends Biotechnol"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Tvaro\u0161ka I (2006) Molecular modeling of retaining glycosyltransferases. In: NMR Spectroscopy and Computer Modeling of Carbohydrates, American Chemical Society, volume 930 of <italic>ACS Symposium Series<\/italic>. pp. 285\u2013301. URL <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/dx.doi.org\/10.1021\/bk-2006-0930.ch016\" xlink:type=\"simple\">http:\/\/dx.doi.org\/10.1021\/bk-2006-0930.ch016<\/ext-link>.","DOI":"10.1021\/bk-2006-0930.ch016"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1146\/annurev.biochem.76.061005.092322","article-title":"Glycosyltransferases: Structures, functions, and mechanisms","volume":"77","author":"L Lairson","year":"2008","journal-title":"Annu Rev Biochem"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"16030","DOI":"10.1021\/ja0659931","article-title":"Chemical rescue of <italic>\u03b1<\/italic>-galactosyltransferase. implications in the mechanism of retaining glycosyltransferases","volume":"128","author":"A Monegal","year":"2006","journal-title":"J Am Chem Soc"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1093\/glycob\/cwq190","article-title":"Trapping and characterization of covalent intermediates of mutant retaining glycosyltransferases","volume":"21","author":"N Soya","year":"2011","journal-title":"Glycobiology"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/S0008-6215(03)00050-8","article-title":"On the reaction pathways and determination of transition-state structures for retaining <italic>\u03b1<\/italic>-galactosyltransferases","volume":"338","author":"I Andr\u00e9","year":"2003","journal-title":"Carbohydr Res"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.carres.2012.03.027","article-title":"Essential role of glutamate 317 in galactosyl transfer by <italic>\u03b1<\/italic>3GalT: a computational study","volume":"356","author":"H G\u00f3mez","year":"2012","journal-title":"Carbohydr Res"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1021\/ja210490f","article-title":"Retaining glycosyltransferase mechanism studied by QM\/MM methods: Lipopolysaccharyl-<italic>\u03b1<\/italic>-1,4-galactosyltransferase C transfers <italic>\u03b1<\/italic>-galactose via an oxocarbenium ion-like transition state","volume":"134","author":"H G\u00f3mez","year":"2012","journal-title":"J Am Chem Soc"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"14018","DOI":"10.1002\/chem.201302898","article-title":"Formation of a covalent glycosyl\u2013enzyme species in a retaining glycosyltransferase","volume":"19","author":"V Rojas-Cervellera","year":"2013","journal-title":"Chem\u2014Eur J"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/nchembio.628","article-title":"Mechanistic evidence for a front-side, SNi-type reaction in a retaining glycosyltransferase","volume":"7","author":"SS Lee","year":"2011","journal-title":"Nat Chem Biol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/84168","article-title":"Crystal structure of the retaining galactosyltransferase LgtC from Neisseria meningitidis in complex with donor and acceptor sugar analogs","volume":"8","author":"K Persson","year":"2001","journal-title":"Nat Struct Mol Biol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.carres.2003.11.014","article-title":"Molecular modeling insights into the catalytic mechanism of the retaining galactosyltransferase LgtC","volume":"339","author":"I Tvaro\u0161ka","year":"2004","journal-title":"Carbohydr Res"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1002\/anie.200905096","article-title":"Mechanistic insight into enzymatic glycosyl transfer with retention of conguration through analysis of glycomimetic inhibitors","volume":"49","author":"JC Errey","year":"2010","journal-title":"Angew Chem, Int Ed"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"10897","DOI":"10.1002\/anie.201104623","article-title":"The molecular mechanism of enzymatic glycosyl transfer with retention of conguration: Evidence for a short-lived oxocarbenium-like species","volume":"50","author":"A Ard\u00e8vol","year":"2011","journal-title":"Angew Chem, Int Ed"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1039\/C3OB42569J","article-title":"A computational and experimental study of O-glycosylation. catalysis by human UDP-GalNAc polypeptide:GalNAc transferase-T2","volume":"12","author":"H G\u00f3mez","year":"2014","journal-title":"Org Biomol Chem"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"24156","DOI":"10.1074\/jbc.270.41.24156","article-title":"Purification and cDNA cloning of a human UDP-N-acetyl-<italic>\u03b1<\/italic>- d-galactosamine:polypeptide N-acetylgalactosaminyltransferase","volume":"270","author":"T White","year":"1995","journal-title":"J Biol Chem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1R","DOI":"10.1093\/glycob\/cwg007","article-title":"All in the family: the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases","volume":"13","author":"KGT Hagen","year":"2003","journal-title":"Glycobiology"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.tcb.2010.11.004","article-title":"Location, location, location: new insights into O-GalNAc protein glycosylation","volume":"21","author":"DJ Gill","year":"2011","journal-title":"Trends Cell Biol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"8613","DOI":"10.1074\/jbc.M513590200","article-title":"Dynamic association between the catalytic and lectin domains of human UDP-GalNAc:polypeptide <italic>\u03b1<\/italic>-N-acetylgalactosaminyltransferase-2","volume":"281","author":"TA Fritz","year":"2006","journal-title":"J Biol Chem"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.jmb.2006.03.061","article-title":"Structural basis of carbohydrate transfer activity by human UDP-GalNAc: Polypeptide <italic>\u03b1<\/italic>-N-acetylgalactosaminyltransferase (pp-GalNAc-T10)","volume":"359","author":"T Kubota","year":"2006","journal-title":"J Mol Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/S0006-291X(02)02549-4","article-title":"Function of the lectin domain of polypeptide N-acetylgalactosaminyltransferase 1","volume":"298","author":"M Tenno","year":"2002","journal-title":"Biochem Biophys Res Commun"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"6797","DOI":"10.1074\/jbc.274.10.6797","article-title":"Structure-function analysis of the UDPN-acetyl-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase","volume":"274","author":"FK Hagen","year":"1999","journal-title":"J Biol Chem"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ijpara.2003.11.016","article-title":"O-glycosylation in toxoplasma gondii: Identification and analysis of a family of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases","volume":"34","author":"MM Stwora-Wojczyk","year":"2004","journal-title":"Int J Parasitol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3390\/i4080503","article-title":"Modelling of octahedral manganese II complexes with inorganic ligands: A problem with spin-states","volume":"4","author":"B Trzaskowski","year":"2003","journal-title":"Int J Mol Sci"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"598","DOI":"10.2478\/s11696-009-0060-4","article-title":"Comparative DFT study on the <italic>\u03b1<\/italic>-glycosidic bond in reactive species of galactosyl diphosphates","volume":"63","author":"J K\u00f3na","year":"2009","journal-title":"Chem Pap"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1042\/BJ20031877","article-title":"Characterization of a UDP-N-acetyl-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase with an unusual lectin domain from the platyhelminth parasite Echinococcus granulosus","volume":"382","author":"T Freire","year":"2004","journal-title":"Biochem J"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1002\/jcc.10255","article-title":"Optimized Slater-type basis sets for the elements 1\u2013118","volume":"24","author":"E Van Lenthe","year":"2003","journal-title":"J Comput Chem"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"5029","DOI":"10.1063\/1.478401","article-title":"Assessment of the Perdew\u2013Burke\u2013Ernzerhof exchange-correlation functional","volume":"110","author":"M Ernzerhof","year":"1999","journal-title":"J Chem Phys"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"6158","DOI":"10.1063\/1.478522","article-title":"Toward reliable density functional methods without adjustable parameters: The PBE0 model","volume":"110","author":"C Adamo","year":"1999","journal-title":"J Chem Phys"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00214-007-0310-x","article-title":"The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals","volume":"120","author":"Y Zhao","year":"2008","journal-title":"Theor Chem Acc"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1021\/ar700111a","article-title":"Density functionals with broad applicability in chemistry","volume":"41","author":"Y Zhao","year":"2008","journal-title":"Acc Chem Res"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1103\/PhysRevA.38.3098","article-title":"Density-functional exchange-energy approximation with correct asymptotic behavior","volume":"38","author":"AD Becke","year":"1988","journal-title":"Phys Rev A"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"8822","DOI":"10.1103\/PhysRevB.33.8822","article-title":"Density-functional approximation for the correlation energy of the inhomogeneous electron gas","volume":"33","author":"JP Perdew","year":"1986","journal-title":"Phys Rev B"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"8206","DOI":"10.1002\/anie.201402781","article-title":"Substrate-guided front-face reaction revealed by combined structural snapshots and metadynamics for the polypeptide N-acetylgalactosaminyltransferase 2","author":"E Lira-Navarrete","year":"2014","journal-title":"Angew Chem Int Ed"},{"key":"ref37","article-title":"ADF2013","author":"EJ Baerends","year":"2013"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1002\/jcc.20857","article-title":"The implementation of a fast and accurate QM\/MM potential method in Amber","volume":"29","author":"RC Walker","year":"2008","journal-title":"J Comput Chem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1002\/jcc.10128","article-title":"Fast, efficient generation of high-quality atomic charges. AM1-BCC model: II. parameterization and validation","volume":"23","author":"A Jakalian","year":"2002","journal-title":"J Comput Chem"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1002\/jcc.1056","article-title":"Chemistry with ADF","volume":"22","author":"G te Velde","year":"2001","journal-title":"J Comput Chem"},{"key":"ref41","first-page":"391","article-title":"Towards an order-N DFT method","volume":"99","author":"C Fonseca Guerra","year":"1998","journal-title":"Theor Chem Acc"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"5179","DOI":"10.1021\/ja00124a002","article-title":"A second generation force field for the simulation of proteins, nucleic acids, and organic molecules","volume":"117","author":"WD Cornell","year":"1995","journal-title":"J Am Chem Soc"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/jcc.20820","article-title":"GLYCAM06: A generalizable biomolecular force field. Carbohydrates","volume":"29","author":"KN Kirschner","year":"2008","journal-title":"J Comput Chem"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/qua.10463","article-title":"AddRemove: A new link model for use in QM\/MM studies","volume":"91","author":"M Swart","year":"2003","journal-title":"Int J Quantum Chem"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/1096-987X(20010115)22:1<79::AID-JCC8>3.0.CO;2-B","article-title":"A charge analysis derived from an atomic multipole expansion","volume":"22","author":"M Swart","year":"2001","journal-title":"J Comput Chem"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/00268970010018431","article-title":"Left-right correlation energy","volume":"99","author":"NC Handy","year":"2001","journal-title":"Mol Phys"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1103\/PhysRevLett.77.3865","article-title":"Generalized gradient approximation made simple","volume":"77","author":"JP Perdew","year":"1996","journal-title":"Phys Rev Lett"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1103\/PhysRevLett.78.1396","article-title":"Generalized gradient approximation made simple [phys. rev. lett. 77, 3865 (1996)]","volume":"78","author":"JP Perdew","year":"1997","journal-title":"Phys Rev Lett"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1002\/jcc.20653","article-title":"Energy landscapes of nucleophilic substitution reactions: A comparison of density functional theory and coupled cluster methods","volume":"28","author":"M Swart","year":"2007","journal-title":"J Comput Chem"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"154104","DOI":"10.1063\/1.3382344","article-title":"A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu","volume":"132","author":"S Grimme","year":"2010","journal-title":"J Chem Phys"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"6670","DOI":"10.1039\/c0cp02984j","article-title":"A thorough benchmark of density functional methods for general main group thermochemistry, kinetics, and noncovalent interactions","volume":"13","author":"L Goerigk","year":"2011","journal-title":"Phys Chem Chem Phys"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1063\/1.454033","article-title":"A multicenter numerical integration scheme for polyatomic molecules","volume":"88","author":"AD Becke","year":"1988","journal-title":"J Chem Phys"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1002\/jcc.23323","article-title":"The Becke fuzzy cells integration scheme in the Amsterdam Density Functional program suite","volume":"34","author":"M Franchini","year":"2013","journal-title":"J Comput Chem"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/0021-9991(92)90277-6","article-title":"Numerical integration for polyatomic systems","volume":"99","author":"G te Velde","year":"1992","journal-title":"J Comput Phys"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S0893-6080(05)80056-5","article-title":"A scaled conjugate gradient algorithm for fast supervised learning","volume":"6","author":"MF M\u00f8ller","year":"1993","journal-title":"Neural Networks"},{"key":"ref56","first-page":"385","article-title":"Classical and Quantum Dynamics in Condensed Phase Simulations","author":"H J\u00f3nsson","year":"1998"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"9978","DOI":"10.1063\/1.1323224","article-title":"Improved tangent estimate in the nudged elastic band method for finding minimum energy paths and saddle points","volume":"113","author":"G Henkelman","year":"2000","journal-title":"J Chem Phys"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1109\/5992.998641","article-title":"An object-oriented scripting interface to a legacy electronic structure code","volume":"4","author":"S Bahn","year":"2002","journal-title":"Comput Sci Eng"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"170201","DOI":"10.1103\/PhysRevLett.97.170201","article-title":"Structural relaxation made simple","volume":"97","author":"E Bitzek","year":"2006","journal-title":"Phys Rev Lett"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1021\/ct400323z","article-title":"A quadratically-converging nudged elastic band optimizer","volume":"9","author":"MU Bohner","year":"2013","journal-title":"J Chem Theory Comput"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jcc.540150102","article-title":"Updated hessian matrix and the restricted step method for locating transition structures","volume":"15","author":"JM Bofill","year":"1994","journal-title":"J Comput Chem"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1021\/ja00839a011","article-title":"General definition of ring puckering coordinates","volume":"97","author":"D Cremer","year":"1975","journal-title":"J Am Chem Soc"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1021\/ci600492e","article-title":"Puckering coordinates of monocyclic rings by triangular decomposition","volume":"47","author":"AD Hill","year":"2007","journal-title":"J Chem Inf Model"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"4308","DOI":"10.1046\/j.1432-1033.2002.03123.x","article-title":"Identification of two cysteine residues involved in the binding of UDP-GalNAc to UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 1 (GalNAc-t1)","volume":"269","author":"M Tenno","year":"2002","journal-title":"Eur J Biochem"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"6037","DOI":"10.1111\/j.1742-4658.2007.06124.x","article-title":"Function of conserved aromatic residues in the Gal\/GalNAc-glycosyltransferase motif of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 1","volume":"274","author":"M Tenno","year":"2007","journal-title":"FEBS J"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004061","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T17:08:19Z","timestamp":1540314499000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004061"}},"subtitle":[],"editor":[{"given":"Helmut","family":"Grubm\u00fcller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,4,7]]},"references-count":65,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,4,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1004061","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,7]]}}}