The structural basis for a coordinated reaction catalyzed by a bifunctional glycosyltransferase in chondroitin biosynthesis

Mack Sobhany, Yoshimitsu Kakuta, Nobuo Sugiura, Koji Kimata, Masahiko Negishi

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Bifunctional chondroitin synthase K4CP catalyzes glucuronic acid and N-acetylgalactosamine transfer activities and polymerizes a chondroitin chain. Here we have determined that an N-terminal region (residues 58-134) coordinates two transfer reactions and enables K4CP to catalyze polymerization. When residues 58-107 are deleted, K4CP loses polymerase activity while retaining both transfer activities. Peptide 113DWPSDL118within this N-terminal region interacts with C-terminal peptide 677YTWEKI 682. The deletion of either sequence abolishes glucuronic acid but not N-acetylgalactosamine transfer activity in K4CP. Both donor bindings and transfer activities are lost by mutating 677YTWEKI682 to 677DAWEDI682. On the other hand, acceptor substrates retain their binding to K4CP mutants. The characteristics of these K4CP mutants highlight different states of the enzyme reaction, providing an underlying structural basis for how these peptides play essential roles in coordinating the two glycosyltransferase activities for K4CP to elongate the chondroitin chain.

Original languageEnglish
Pages (from-to)36022-36028
Number of pages7
JournalJournal of Biological Chemistry
Volume287
Issue number43
DOIs
Publication statusPublished - Oct 19 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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