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Here, cysteine thiol modifications were characterized based on protein microenvironments, secondary structures and specific protein functions. Protein microenvironment around an amino acid was defined as the summation of hydrophobic contributions from the surrounding protein fragments and the solvent molecules present within its first contact shell. Cysteine functions (modifications) were grouped into enzymatic and non\u2010enzymatic classes. Modifications studied were\u2014disulfide formation, thio\u2010ether formation, metal\u2010binding, nitrosylation, acylation, selenylation, glutathionylation, sulfenylation, and ribosylation. 1079 enzymatic proteins were reported from high\u2010resolution crystal structures. Protein microenvironments around cysteine thiol, derived from above crystal structures, were clustered into 3 groups\u2014buried\u2010hydrophobic, intermediate and exposed\u2010hydrophilic clusters. Characterization of cysteine functions were statistically meaningful for 4 modifications (disulfide formation, thioether formation, sulfenylation, and iron\/zinc binding) those have sufficient amount of data in the current dataset. Results showed that protein microenvironment, secondary structure and protein functions were conserved for enzymatic cysteine functions, in contrast to the same function from non\u2010enzymatic cysteines. Disulfide forming enzymatic cysteines were tightly packed within intermediate protein microenvironment cluster, have alpha\u2010helical conformation and mostly belonged to CxxC motif of electron transport proteins. Disulfide forming non\u2010enzymatic cysteines did not belong to conserved motif and have variable secondary structures. Similarly, enzymatic thioether forming cysteines have conserved microenvironment compared to non\u2010enzymatic cystienes. Based on the compatibility between protein microenvironment and cysteine modifications, more efficient drug molecules could be designed against cysteine\u2010related diseases.<\/jats:p>","DOI":"10.1002\/prot.25424","type":"journal-article","created":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T08:36:42Z","timestamp":1510735002000},"page":"192-209","source":"Crossref","is-referenced-by-count":18,"title":["Characterization of cysteine thiol modifications based on protein microenvironments and local secondary structures"],"prefix":"10.1002","volume":"86","author":[{"given":"Akshay","family":"Bhatnagar","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Birla Institute of Technology and Science, Pilani Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4131-907X","authenticated-orcid":false,"given":"Debashree","family":"Bandyopadhyay","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Birla Institute of Technology and Science, Pilani Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,11,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540211468"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(03)00174-1"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200300573"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2005.09.006"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2010.07576.x"},{"key":"e_1_2_6_7_1","volume-title":"Inorganic Chemistry","author":"Jones W.","year":"1949"},{"key":"e_1_2_6_8_1","volume-title":"General Chemistry","author":"Pauling L.","year":"1988"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400496200"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3376"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(87)43023-1"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(99)76868-2"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.23098"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4476"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-7658-7"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms14010434"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201101024"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R113.461368"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M213125200"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200104008"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.263525"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903015106"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21958"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.25101"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21287"},{"key":"e_1_2_6_27_1","volume-title":"The Hydrophobic Fragmental Constant","year":"1977"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540151009"},{"key":"e_1_2_6_29_1","volume-title":"Cluster Analysis","author":"Tryon DE","year":"1973"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00357-014-9161-z"},{"key":"e_1_2_6_31_1","unstructured":"Addinsoft. 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