{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:40:46Z","timestamp":1787985646936,"version":"build-2784847793"},"reference-count":33,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,12,15]]},"abstract":"<jats:p>Bilirubin glucuronidation, catalysed by UGT1A1 [UGT (UDP glucuronosyltransferase) isoform 1A1, EC 2.4.1.17], is critical for biliary elimination of bilirubin. UGT1A1 deficiency causes CN-1 (Crigler\u2013Najjar syndrome type\u00a01), which is characterized by potentially lethal unconjugated hyperbilirubinaemia. Nucleotide sequence analysis of UGT1A1 in two CN-1 patients revealed that patient A was homozygous for a nt 530 G\u2192A (where nt 530 G\u2192A means guanine to adenine transition at nucleotide 530) mutation, predicting a C177Y substitution, and patient B had a nt 466 T\u2192C mutation on one allele and a nt 1070 A\u2192G mutation on the other, predicting a C156R and a Q357R substitution respectively. All 11 cysteine residues of mature human UGT1A1 are highly conserved in other human UGT isoforms and in rat, mouse and Rhesus monkey UGT1A1, suggesting their functional importance. Expression of mutagenized UGT1A1 plasmids showed that substitution of any of the seven cysteine residues located within the endoplasmic reticulum cisternae (including those mutated in patients A and B) abolished UGT1A1 activity or markedly increased its apparent Km for bilirubin. Substitution of the three cysteine residues within the C-terminal cytosolic tail had minimal effect on basal UGT1A1 activity, but prevented UGT1A1 activation by UDP-GlcNAc. N-Ethylmaleimide did not inhibit UGT1A1 activity in native microsomes, but prevented UGT1A1 activation by UDP-GlcNAc and inhibited the activity in digitonin-permeabilized microsomes. Dithiothreitol did not affect UGT1A1 activity in human liver microsomes. Together, the results suggested that free thiol groups, but not disulphide bonding, of seven cysteine residues within the intracisternal region of human UGT1A1 are important for its catalytic activity, while cysteine residues in the cytosolic domain may be involved in its physiological activation by UDP-GlcNAc.<\/jats:p>","DOI":"10.1042\/bj20050381","type":"journal-article","created":{"date-parts":[[2005,12,6]],"date-time":"2005-12-06T15:22:20Z","timestamp":1133882540000},"page":"685-692","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Role of cysteine residues in the function of human UDP glucuronosyltransferase isoform 1A1 (UGT1A1)"],"prefix":"10.1042","volume":"392","author":[{"given":"Siddhartha\u00a0S.","family":"Ghosh","sequence":"first","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."},{"name":"Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."},{"name":"Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung\u00a0W.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."},{"name":"Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."},{"name":"Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandan","family":"Guha","sequence":"additional","affiliation":[{"name":"Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."},{"name":"Department of Radiation Oncology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayanta","family":"Roy-Chowdhury","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."},{"name":"Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."},{"name":"Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namita","family":"Roy-Chowdhury","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."},{"name":"Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."},{"name":"Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2005,12,6]]},"reference":[{"key":"2021112213125024100_B1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/262326a0","article-title":"Structure of bilirubin","volume":"262","author":"Bonnett","year":"1976","journal-title":"Nature (London)"},{"key":"2021112213125024100_B2","first-page":"3063","article-title":"Hereditary jaundice and disorders of bilirubin metabolism","volume-title":"The Metabolic Basis of Inherited Disease","author":"Roy\u00a0Chowdhury","year":"2001","edition":"8th edn"},{"key":"2021112213125024100_B3","doi-asserted-by":"crossref","first-page":"17960","DOI":"10.1016\/S0021-9258(17)32403-1","article-title":"Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man","volume":"269","author":"Bosma","year":"1994","journal-title":"J. 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