The N-terminal of human UGT1A6 is on the outside, as evidenced by ELISA with autoantibody in autoimmune hepatitis sera.

Abstract

Sera from AIH (autoimmune hepatitis) type 2 patients contain an autoantibody against the UGT1A subtype, called anti-LKM3. Previously, we reported that sera in AIH type 1 patients contained autoantibodies against drug-metabolizing enzymes (Shinoda et al. (2004) Autoimmunity, 37, 473). In this report, we showed that AIH-1 sera did not react with some peptides in the C-terminal half of the UGT1A subtype but reacted with a peptide P1(33-42) among several common peptides in the N-terminal half of the UGT1A subtype. This result suggests that the P1 site (33-42) presents on the outside of the UGT1A molecule to be recognized by lymphocytes of the immune system to produce an autoantibody. To detect a key recognition site on peptide P1(33-42), we studied the reactivity of two peptides, M1(28-37) and M2(38-47), containing the N-terminal and C-terminal half of peptide P1. Peptide M2 did not react with AIH-1 serum but peptide M1 did. Thus, the common peptide sequence 33-37 in the positive peptide M1(28-37) and P1(33-42) is a key recognition sequence. Next, we studied the reactivity of some other synthetic peptides, in which some amino acids in the sequence 33-37 in peptide M1 changed to Ala. The peptides changing to Ala (PQ33-34AA) or (DGS35-37AAA) did not react with AIH-1 sera. Meanwhile, these AIH sera did not inhibit the glucuronidation of p-nitrophenol by UGT1A6, suggesting that the key sequence 33-37 might not be contained in active sites of glucuronidation by UGT1A6. In conclusion, sera from AIH-1 patients reacted with the amino acids in the sequence 33-37 (PQDGS) of the N-terminal of UGT1A6.

• Authors: Hitomi Mori, Masakazu Shinoda, Takaharu Mizutani
• Journal: Drug metabolism letters (Drug Metab Lett) Vol. 1 Issue 4 Pg. 261-6 (Dec 2007) ISSN: 1874-0758 [Electronic] United Arab Emirates
• PMID: 19356052 (Publication Type: Journal Article)

Chemical References

• Autoantibodies
• Glucuronides
• Nitrophenols
• Peptides
• UDP-glucuronosyltransferase, UGT1A6
• Glucuronosyltransferase
• 4-nitrophenol

Topics

• Amino Acid Sequence
• Autoantibodies (immunology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Glucuronides (metabolism)
• Glucuronosyltransferase (immunology)
• Hepatitis, Autoimmune (immunology)
• Humans
• Lymphocytes (immunology)
• Middle Aged
• Nitrophenols (metabolism)
• Peptides (chemistry)