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PDBsum entry 2q1f
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* Residue conservation analysis
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Enzyme class:
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E.C.4.2.2.21
- chondroitin-sulfate-ABC exolyase.
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Glycobiology
18:270-277
(2008)
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PubMed id:
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Composite active site of chondroitin lyase ABC accepting both epimers of uronic acid.
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D.Shaya,
B.S.Hahn,
T.M.Bjerkan,
W.S.Kim,
N.Y.Park,
J.S.Sim,
Y.S.Kim,
M.Cygler.
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ABSTRACT
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Enzymes have evolved as catalysts with high degrees of stereospecificity. When
both enantiomers are biologically important, enzymes with two different folds
usually catalyze reactions with the individual enantiomers. In rare cases a
single enzyme can process both enantiomers efficiently, but no molecular basis
for such catalysis has been established. The family of bacterial chondroitin
lyases ABC comprises such enzymes. They can degrade both chondroitin sulfate
(CS) and dermatan sulfate (DS) glycosaminoglycans at the nonreducing end of
either glucuronic acid (CS) or its epimer iduronic acid (DS) by a
beta-elimination mechanism, which commences with the removal of the C-5 proton
from the uronic acid. Two other structural folds evolved to perform these
reactions in an epimer-specific fashion: (alpha/alpha)(5) for CS (chondroitin
lyases AC) and beta-helix for DS (chondroitin lyases B); their catalytic
mechanisms have been established at the molecular level. The structure of
chondroitinase ABC from Proteus vulgaris showed surprising similarity to
chondroitinase AC, including the presence of a Tyr-His-Glu-Arg catalytic tetrad,
which provided a possible mechanism for CS degradation but not for DS
degradation. We determined the structure of a distantly related Bacteroides
thetaiotaomicron chondroitinase ABC to identify additional structurally
conserved residues potentially involved in catalysis. We found a conserved
cluster located approximately 12 A from the catalytic tetrad. We demonstrate
that a histidine in this cluster is essential for catalysis of DS but not CS.
The enzyme utilizes a single substrate-binding site while having two partially
overlapping active sites catalyzing the respective reactions. The spatial
separation of the two sets of residues suggests a substrate-induced
conformational change that brings all catalytically essential residues close
together.
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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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Z.H.Elmabrouk,
F.Vincent,
M.Zhang,
N.L.Smith,
J.P.Turkenburg,
S.J.Charnock,
G.W.Black,
and
E.J.Taylor
(2011).
Crystal structures of a family 8 polysaccharide lyase reveal open and highly occluded substrate-binding cleft conformations.
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Proteins,
79,
965-974.
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PDB codes:
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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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V.Lombard,
T.Bernard,
C.Rancurel,
H.Brumer,
P.M.Coutinho,
and
B.Henrissat
(2010).
A hierarchical classification of polysaccharide lyases for glycogenomics.
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Biochem J,
432,
437-444.
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V.Prabhakar,
I.Capila,
V.Soundararajan,
R.Raman,
and
R.Sasisekharan
(2009).
Recombinant expression, purification, and biochemical characterization of chondroitinase ABC II from Proteus vulgaris.
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J Biol Chem,
284,
974-982.
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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.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
