Structural analysis of sialyltransferase PM0188 from Pasteurella multocida complexed with donor analogue and acceptor sugar

Dong Uk Kim, Ji Ho Yoo, Joo Lee Yong, Soo Kim Kwan, Hyun Soo Cho

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

PM0188 is a newly identified sialyltransferase from P. multocida which transfers sialic acid from cytidine 5′-monophosphonuraminic acid (CMP-NeuAc) to an acceptor sugar. Although sialyltransferases are involved in important biological functions like cell-cell recognition, cell differentiation and receptor-ligand interactions, little is known about their catalytic mechanism. Here, we report the X-ray crystal structures of PM0188 in the presence of an acceptor sugar and a donor sugar analogue, revealing the precise mechanism of sialic acid transfer. Site-directed mutagenesis, kinetic assays, and structural analysis show that Asp141, His311, Glu338, Ser355 and Ser356 are important catalytic residues; Asp141 is especially crucial as it acts as a general base. These complex structures provide insights into the mechanism of sialyltransferases and the structure-based design of specific inhibitors.

Original languageEnglish
Pages (from-to)48-54
Number of pages7
JournalJournal of Biochemistry and Molecular Biology
Volume41
Issue number1
Publication statusPublished - 2008 Jan 1

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Sialyltransferases
Pasteurella multocida
Structural analysis
Sugars
N-Acetylneuraminic Acid
Cytidine Monophosphate
Cytidine
Mutagenesis
Site-Directed Mutagenesis
Cell Differentiation
Assays
Crystal structure
X-Rays
Ligands
X rays
Kinetics
Acids

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

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abstract = "PM0188 is a newly identified sialyltransferase from P. multocida which transfers sialic acid from cytidine 5′-monophosphonuraminic acid (CMP-NeuAc) to an acceptor sugar. Although sialyltransferases are involved in important biological functions like cell-cell recognition, cell differentiation and receptor-ligand interactions, little is known about their catalytic mechanism. Here, we report the X-ray crystal structures of PM0188 in the presence of an acceptor sugar and a donor sugar analogue, revealing the precise mechanism of sialic acid transfer. Site-directed mutagenesis, kinetic assays, and structural analysis show that Asp141, His311, Glu338, Ser355 and Ser356 are important catalytic residues; Asp141 is especially crucial as it acts as a general base. These complex structures provide insights into the mechanism of sialyltransferases and the structure-based design of specific inhibitors.",
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Structural analysis of sialyltransferase PM0188 from Pasteurella multocida complexed with donor analogue and acceptor sugar. / Kim, Dong Uk; Yoo, Ji Ho; Yong, Joo Lee; Kwan, Soo Kim; Cho, Hyun Soo.

In: Journal of Biochemistry and Molecular Biology, Vol. 41, No. 1, 01.01.2008, p. 48-54.

Research output: Contribution to journalArticle

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