{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:32:28Z","timestamp":1748478748046},"reference-count":22,"publisher":"World Scientific Pub Co Pte Ltd","issue":"06","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Bioinform. Comput. Biol."],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:p>Fumarase catalyzes the reversible, stereospecific hydration\/dehydration of fumarate to L-malate during the Kreb\u2019s cycle. In the crystal structure of the tetrameric fumarase, it was found that some of the active site residues S145, T147, N188 G364 and H235 had water-mediated hydrogen bonding interactions with pyromellitic acid and citrate which help to the protonation state for the conversion of fumarate to malate. When His 235 is mutated with Asn (H235N), water-mediated interactions were lost due to the shifting of active site water molecule by 0.7 \u00c5 away. Molecular dynamics (MD) simulations were also carried out by NAMD and analyzed using Assisted Model Building with Energy Refinement (AMBER) program to better understand the conformational stability and other aspects during the binding of pyromellitic acid and citrate with native and mutant FH. The role of hydrogen bonds and hydrophobic interactions was also analyzed. The present study confirms that the H235N mutation has a major effect on the catalytic activity of fumarase which is evident from the biochemical studies.<\/jats:p>","DOI":"10.1142\/s0219720017500263","type":"journal-article","created":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T06:33:05Z","timestamp":1510641185000},"page":"1750026","source":"Crossref","is-referenced-by-count":4,"title":["Molecular docking and molecular dynamics simulations of fumarate hydratase and its mutant H235N complexed with pyromellitic acid and citrate"],"prefix":"10.1142","volume":"15","author":[{"given":"S.","family":"Subasri","sequence":"first","affiliation":[{"name":"Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Chennai 600 025, India"}]},{"given":"Santosh Kumar","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Department of Physics, Indian Institute of Science, Bangalore 560 012, India"}]},{"given":"K.","family":"Sekar","sequence":"additional","affiliation":[{"name":"Department of Computational and Data Sciences, Indian Institute of Science, Bangalore 560 012, India"}]},{"given":"Manish","family":"Kesherwani","sequence":"additional","affiliation":[{"name":"Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Chennai 600 025, India"}]},{"given":"D.","family":"Velmurugan","sequence":"additional","affiliation":[{"name":"Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Chennai 600 025, India"}]}],"member":"219","published-online":{"date-parts":[[2017,12,12]]},"reference":[{"key":"S0219720017500263BIB001","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9294-8"},{"key":"S0219720017500263BIB002","doi-asserted-by":"publisher","DOI":"10.1110\/ps.0201502"},{"issue":"16","key":"S0219720017500263BIB003","volume":"36","author":"Subasri S","year":"2017","journal-title":"J Biomol Struct Dyn"},{"key":"S0219720017500263BIB004","doi-asserted-by":"publisher","DOI":"10.1042\/bj2370547"},{"key":"S0219720017500263BIB005","doi-asserted-by":"publisher","DOI":"10.1038\/nsb1094-724"},{"key":"S0219720017500263BIB006","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0895-654"},{"key":"S0219720017500263BIB007","doi-asserted-by":"publisher","DOI":"10.1021\/bi9614702"},{"key":"S0219720017500263BIB008","first-page":"1395","volume":"61","author":"Weaver T","year":"2005","journal-title":"Actacryst"},{"key":"S0219720017500263BIB009","doi-asserted-by":"crossref","first-page":"6270","DOI":"10.1016\/S0021-9258(18)63533-1","volume":"244","author":"Hansen JN","year":"1969","journal-title":"J Biol Chem"},{"key":"S0219720017500263BIB010","doi-asserted-by":"publisher","DOI":"10.1021\/bi00156a019"},{"key":"S0219720017500263BIB011","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560060410"},{"key":"S0219720017500263BIB013","doi-asserted-by":"publisher","DOI":"10.1063\/1.445869"},{"key":"S0219720017500263BIB014","doi-asserted-by":"publisher","DOI":"10.1021\/jm050540c"},{"key":"S0219720017500263BIB015","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20289"},{"key":"S0219720017500263BIB016","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20290"},{"key":"S0219720017500263BIB017","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20035"},{"key":"S0219720017500263BIB018","doi-asserted-by":"publisher","DOI":"10.1063\/1.464397"},{"key":"S0219720017500263BIB019","doi-asserted-by":"publisher","DOI":"10.1021\/ct9001015"},{"key":"S0219720017500263BIB020","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9991(77)90098-5"},{"key":"S0219720017500263BIB021","doi-asserted-by":"publisher","DOI":"10.1063\/1.470648"},{"key":"S0219720017500263BIB022","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20033"},{"key":"S0219720017500263BIB023","doi-asserted-by":"publisher","DOI":"10.1021\/ct300418h"}],"container-title":["Journal of Bioinformatics and Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.worldscientific.com\/doi\/pdf\/10.1142\/S0219720017500263","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T05:51:59Z","timestamp":1659851519000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.worldscientific.com\/doi\/abs\/10.1142\/S0219720017500263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12]]},"references-count":22,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2017,12,12]]},"published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1142\/S0219720017500263"],"URL":"https:\/\/doi.org\/10.1142\/s0219720017500263","relation":{},"ISSN":["0219-7200","1757-6334"],"issn-type":[{"value":"0219-7200","type":"print"},{"value":"1757-6334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12]]}}}