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Cytidine 5'-monophosphate (CMP)-induced structural changes in a multifunctional sialyltransferase from Pasteurella
Lisheng Ni1, Mingchi Sun, Hai Yu
1Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616, USA.
Biochemistry
|February 16, 2006
Summary
This study reveals the novel structure of Pasteurella multocida sialyltransferase (PmST1), a key enzyme in synthesizing crucial glycoconjugates. The crystal structure shows a unique two-domain arrangement and a distinct CMP binding mechanism.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Sialyltransferases are crucial enzymes synthesizing sialic acid-containing molecules involved in physiological and pathological processes.
- Understanding their structure is vital for elucidating their function and developing therapeutic strategies.
Purpose of the Study:
- To determine the crystal structure of a truncated Pasteurella multocida sialyltransferase (Delta24PmST1).
- To investigate the structural basis of CMP binding and its effect on enzyme conformation.
Main Methods:
- X-ray crystallography was employed to determine the structures of Delta24PmST1 in the absence and presence of CMP.
- Structural analysis focused on domain organization, nucleotide binding site, and conformational changes upon ligand binding.
Main Results:
- The Delta24PmST1 structure reveals two distinct Rossmann nucleotide-binding domains, classifying it as a glycosyltransferase-B (GT-B) type enzyme.
- Unlike other GT-B enzymes, Delta24PmST1 lacks a C-terminal extension interacting with the N-terminal domain.
- CMP binding induces a significant conformational change, closing the gap between the two domains via specific residue interactions and a water molecule bridge.
Conclusions:
- Delta24PmST1 represents a novel GT-B structural type with a unique inter-domain communication mechanism.
- The observed conformational change upon CMP binding likely primes the enzyme for acceptor substrate binding and catalysis.