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PDBsum entry 3ilr
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Enzyme class:
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E.C.4.2.2.7
- heparin lyase.
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Reaction:
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Eliminative cleavage of polysaccharides containing 1,4-linked glucuronate or iduronate residues and 1,4-alpha-linked 2-sulfoamino-2-deoxy-6-sulfo- D-glucose residues to give oligosaccharides with terminal 4-deoxy-alpha- D-gluc-4-enuronosyl groups at their non-reducing ends.
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DOI no:
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J Biol Chem
284:34019-34027
(2009)
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PubMed id:
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Structural snapshots of heparin depolymerization by heparin lyase I.
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Y.H.Han,
M.L.Garron,
H.Y.Kim,
W.S.Kim,
Z.Zhang,
K.S.Ryu,
D.Shaya,
Z.Xiao,
C.Cheong,
Y.S.Kim,
R.J.Linhardt,
Y.H.Jeon,
M.Cygler.
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ABSTRACT
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Heparin lyase I (heparinase I) specifically depolymerizes heparin, cleaving the
glycosidic linkage next to iduronic acid. Here, we show the crystal structures
of heparinase I from Bacteroides thetaiotaomicron at various stages of the
reaction with heparin oligosaccharides before and just after cleavage and
product disaccharide. The heparinase I structure is comprised of a
beta-jellyroll domain harboring a long and deep substrate binding groove and an
unusual thumb-resembling extension. This thumb, decorated with many basic
residues, is of particular importance in activity especially on short heparin
oligosaccharides. Unexpected structural similarity of the active site to that of
heparinase II with an (alpha/alpha)(6) fold is observed. Mutational studies and
kinetic analysis of this enzyme provide insights into the catalytic mechanism,
the substrate recognition, and processivity.
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Selected figure(s)
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Figure 1.
Overall structures of heparinase I. A, degradation of heparin
and heparin sulfate by heparinases I–III. The naming of the
sugar sites follows the nomenclature introduced by Davies et al.
(26). The arrows indicate the cleavage site. B, schematic
representation of the heparinase I-H151A-heparin oligosaccharide
(HE[12]) complex. The heparin is shown in stick representation,
and Ca^2+ is shown as an orange sphere. The thumb domain is
colored blue, and the tip of the thumb (indicated by the blue
arrow) is colored cyan. C, close-up of the thumb domain rainbow
(blue, N terminus; red, C terminus). D, bipyramidal coordination
of a Ca^2+ ion in apo heparinase I structure. These and
subsequent figures were prepared with PyMOL (27).
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Figure 8.
Superposition of the active site of heparinases I and II.
Heparinase I is shown in green, and heparinase II is shown in
cyan (Protein Data Bank code 2FUT). The Tyr and His residues and
the IdoA in the +1 site superimpose very well. The carboxylic
group of IdoA is stabilized by Gln and Lys in heparinase I and
by Glu and Arg in heparinase II.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2009,
284,
34019-34027)
copyright 2009.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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M.L.Garron,
and
M.Cygler
(2010).
Structural and mechanistic classification of uronic acid-containing polysaccharide lyases.
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Glycobiology,
20,
1547-1573.
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Z.Wang,
M.Ly,
F.Zhang,
W.Zhong,
A.Suen,
A.M.Hickey,
J.S.Dordick,
and
R.J.Linhardt
(2010).
E. coli K5 fermentation and the preparation of heparosan, a bioengineered heparin precursor.
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Biotechnol Bioeng,
107,
964-973.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
