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PDBsum entry 4js2
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PDB id:
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Transferase
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Title:
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Crystal structure of human beta-galactoside alpha-2,6- sialyltransferase 1 in complex with cmp
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Structure:
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Beta-galactoside alpha-2,6-sialyltransferase 1. Chain: a. Fragment: catalytic domain, unp residues 89-406. Synonym: alpha 2,6-st 1, b-cell antigen cd75, cmp-n- acetylneuraminate-beta-galactosamide-alpha-2,6-sialyltransferase 1, st6gal i, st6gali, sialyltransferase 1. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: st6gal1, siat1. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek 293
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Resolution:
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2.30Å
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R-factor:
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0.177
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R-free:
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0.213
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Authors:
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B.Kuhn,J.Benz,M.Greif,A.M.Engel,H.Sobek,M.G.Rudolph
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Key ref:
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B.Kuhn
et al.
(2013).
The structure of human α-2,6-sialyltransferase reveals the binding mode of complex glycans.
Acta Crystallogr D Biol Crystallogr,
69,
1826-1838.
PubMed id:
DOI:
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Date:
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22-Mar-13
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Release date:
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31-Jul-13
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PROCHECK
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Headers
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References
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P15907
(SIAT1_HUMAN) -
Beta-galactoside alpha-2,6-sialyltransferase 1 from Homo sapiens
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Seq:
Struc:
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406 a.a.
318 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.2.4.3.1
- beta-galactoside alpha-(2,6)-sialyltransferase.
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Reaction:
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a beta-D-galactoside + CMP-N-acetyl-beta-neuraminate = an N-acetyl-alpha- neuraminyl-(2->6)-beta-D-galactosyl derivative + CMP + H+
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beta-D-galactoside
Bound ligand (Het Group name = )
matches with 84.62% similarity
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+
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CMP-N-acetyl-beta-neuraminate
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=
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N-acetyl-alpha- neuraminyl-(2->6)-beta-D-galactosyl derivative
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+
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CMP
Bound ligand (Het Group name = )
corresponds exactly
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Acta Crystallogr D Biol Crystallogr
69:1826-1838
(2013)
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PubMed id:
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The structure of human α-2,6-sialyltransferase reveals the binding mode of complex glycans.
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B.Kuhn,
J.Benz,
M.Greif,
A.M.Engel,
H.Sobek,
M.G.Rudolph.
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ABSTRACT
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Human β-galactoside α-2,6-sialyltransferase I (ST6Gal-I) establishes the final
glycosylation pattern of many glycoproteins by transferring a sialyl moiety to a
terminal galactose. Complete sialylation of therapeutic immunoglobulins is
essential for their anti-inflammatory activity and protein stability, but is
difficult to achieve in vitro owing to the limited activity of ST6Gal-I towards
some galactose acceptors. No structural information on ST6Gal-I that could help
to improve the enzymatic properties of ST6Gal-I for biotechnological purposes is
currently available. Here, the crystal structures of human ST6Gal-I in complex
with the product cytidine 5'-monophosphate and in complex with cytidine and
phosphate are described. These complexes allow the rationalization of the
inhibitory activity of cytosine-based nucleotides. ST6Gal-I adopts a variant of
the canonical glycosyltransferase A fold and differs from related
sialyltransferases by several large insertions and deletions that determine its
regiospecificity and substrate specificity. A large glycan from a symmetry mate
localizes to the active site of ST6Gal-I in an orientation compatible with
catalysis. The glycan binding mode can be generalized to any glycoprotein that
is a substrate of ST6Gal-I. Comparison with a bacterial sialyltransferase in
complex with a modified sialyl donor lends insight into the Michaelis complex.
The results support an SN2 mechanism with inversion of configuration at the
sialyl residue and suggest substrate-assisted catalysis with a charge-relay
mechanism that bears a conceptual similarity to serine proteases.
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