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PDBsum entry 2ex0
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References listed in PDB file
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Key reference
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Title
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Cytidine 5'-Monophosphate (cmp)-Induced structural changes in a multifunctional sialyltransferase from pasteurella multocida.
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Authors
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L.Ni,
M.Sun,
H.Yu,
H.Chokhawala,
X.Chen,
A.J.Fisher.
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Ref.
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Biochemistry, 2006,
45,
2139-2148.
[DOI no: ]
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PubMed id
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Abstract
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Sialyltransferases catalyze reactions that transfer a sialic acid from
CMP-sialic acid to an acceptor (a structure terminated with galactose,
N-acetylgalactosamine, or sialic acid). They are key enzymes that catalyze the
synthesis of sialic acid-containing oligosaccharides, polysaccharides, and
glycoconjugates that play pivotal roles in many critical physiological and
pathological processes. The structures of a truncated multifunctional
Pasteurella multocida sialyltransferase (Delta24PmST1), in the absence and
presence of CMP, have been determined by X-ray crystallography at 1.65 and 2.0 A
resolutions, respectively. The Delta24PmST1 exists as a monomer in solution and
in crystals. Different from the reported crystal structure of a bifunctional
sialyltransferase CstII that has only one Rossmann domain, the overall structure
of the Delta24PmST1 consists of two separate Rossmann nucleotide-binding
domains. The Delta24PmST1 structure, thus, represents the first
sialyltransferase structure that belongs to the glycosyltransferase-B (GT-B)
structural group. Unlike all other known GT-B structures, however, there is no
C-terminal extension that interacts with the N-terminal domain in the
Delta24PmST1 structure. The CMP binding site is located in the deep cleft
between the two Rossmann domains. Nevertheless, the CMP only forms interactions
with residues in the C-terminal domain. The binding of CMP to the protein causes
a large closure movement of the N-terminal Rossmann domain toward the C-terminal
nucleotide-binding domain. Ser 143 of the N-terminal domain moves up to
hydrogen-bond to Tyr 388 of the C-terminal domain. Both Ser 143 and Tyr 388 form
hydrogen bonds to a water molecule, which in turn hydrogen-bonds to the terminal
phosphate oxygen of CMP. These interactions may trigger the closure between the
two domains. Additionally, a short helix near the active site seen in the apo
structure becomes disordered upon binding to CMP. This helix may swing down upon
binding to donor CMP-sialic acid to form the binding pocket for an acceptor.
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