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PDBsum entry 1cb8
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of chondroitin ac lyase, A representative of a family of glycosaminoglycan degrading enzymes.
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Authors
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J.Féthière,
B.Eggimann,
M.Cygler.
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Ref.
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J Mol Biol, 1999,
288,
635-647.
[DOI no: ]
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PubMed id
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Abstract
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Glycosaminoglycans (GAGs), highly sulfated polymers built of hexosamine-uronic
acid disaccharide units, are major components of the extracellular matrix,
mostly in the form of proteoglycans. They interact with a large array of
proteins, in particular of the blood coagulation cascade. Degradation of GAGs in
mammalian systems occurs by the action of GAG hydrolases. Bacteria express a
large number of GAG-degrading lyases that break the hexosamine-uronic acid bond
to create an unsaturated sugar ring. Flavobacterium heparinum produces at least
five GAG lyases of different specificity. Chondroitin AC lyase (chondroitinase
AC, 75 kDa) is highly active toward chondroitin 4-sulfate and chondroitin-6
sulfate. Its crystal structure has been determined to 1.9 A resolution. The
enzyme is composed of two domains. The N-terminal domain of approximately 300
residues contains mostly alpha-helices which form a doubly-layered horseshoe (a
subset of the (alpha/alpha)6 toroidal topology). The approximately 370 residues
long C-terminal domain is made of beta-strands arranged in a four layered
beta-sheet sandwich, with the first two sheets having nine strands each. This
fold is novel and has no counterpart in full among known structures. The
sequence of chondroitinase AC shows low level of homology to several hyaluronate
lyases, which likely share its fold. The shape of the molecule, distribution of
electrostatic potential, the pattern of conservation of the amino acids and the
results of mutagenesis of hyaluronate lyases, indicate that the enzymatic
activity resides primarily within the N-terminal domain. The most likely
candidate for the catalytic base is His225. Other residues involved in catalysis
and/or substrate binding are Arg288, Arg292, Lys298 and Lys299.
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Figure 5.
Figure 5. The pentagonal bipyramidal coordination of
the Ca
2+
. Asp416 and Wat702 are in axial positions.
Ca+2 is shown in orange, oxygen atoms in red, nitrogen
atoms in blue. The residues involved in coordination are
shown in full. The loop around calcium is shown as a
C
a
trace. The magenta arrow indicates the short central
b-strand of the sheet S1. Figure prepared with Raster3D
(Merritt & Bacon, 1997).
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Figure 6.
Figure 6. The electron density extending from the
side-chain of Ser455. Modeled carbohydrate is shown in
thick lines.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1999,
288,
635-647)
copyright 1999.
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Secondary reference #1
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Title
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Crystallization and preliminary analysis of chondroitinase ac from flavobacterium heparinum.
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Authors
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J.Féthière,
B.H.Shilton,
Y.Li,
M.Allaire,
M.Laliberté,
B.Eggimann,
M.Cygler.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 1998,
54,
279-280.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1 Tetragonal crystal of chondroitinase AC from F.
heparinum.
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The above figure is
reproduced from the cited reference
with permission from the IUCr
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