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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.2.1.18
- Exo-alpha-sialidase.
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Reaction:
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Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)-glycosidic linkages of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates.
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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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1 term
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Biological process
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metabolic process
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2 terms
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Biochemical function
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hydrolase activity
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6 terms
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DOI no:
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Chembiochem
6:1999-2004
(2005)
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PubMed id:
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Two nucleophilic mutants of the Micromonospora viridifaciens sialidase operate with retention of configuration by two different mechanisms.
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J.N.Watson,
S.Newstead,
A.A.Narine,
G.Taylor,
A.J.Bennet.
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ABSTRACT
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Mutants of the Micromonospora viridifaciens sialidase, Y370E and Y370F, are
catalytically active retaining enzymes that operate by different mechanisms.
Previous substitutions with smaller amino acids, including Y370D, yielded
inverting sialidases. At least one water molecule can fit into the active-site
cavity of this mutant and act as a nucleophile from the face opposite the
leaving group (Biochemistry 2003, 42, 12 682). Thus, addition of a CH(2) unit
(Asp versus Glu) changes the mechanism from inversion back to retention of
configuration. Based on Brønsted beta(lg) values, it is proposed that the Y370E
mutant reacts by a double-displacement mechanism (beta(lg) on k(cat)/K(m)
-0.36+/-0.04) with Glu370 acting as the nucleophile. However, the Y370F mutant
(beta(lg) on k(cat)/K(m) -0.79+/-0.12) reacts via a dissociative transition
state. The crystal structure of the Y370F mutant complexed with
2-deoxy-2,3-dehydro-N-acetylneuraminic acid shows no significant active-site
perturbation relative to the wild-type enzyme.
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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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A.Albohy,
M.D.Li,
R.B.Zheng,
C.Zou,
and
C.W.Cairo
(2010).
Insight into substrate recognition and catalysis by the human neuraminidase 3 (NEU3) through molecular modeling and site-directed mutagenesis.
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Glycobiology, 20,
1127-1138.
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S.T.Carvalho,
M.Sola-Penna,
I.A.Oliveira,
S.Pita,
A.S.Gonçalves,
B.C.Neves,
F.R.Sousa,
L.Freire-de-Lima,
M.Kurogochi,
H.Hinou,
S.Nishimura,
L.Mendonça-Previato,
J.O.Previato,
and
A.R.Todeschini
(2010).
A new class of mechanism-based inhibitors for Trypanosoma cruzi trans-sialidase and their influence on parasite virulence.
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Glycobiology, 20,
1034-1045.
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A.Buschiazzo,
and
P.M.Alzari
(2008).
Structural insights into sialic acid enzymology.
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Curr Opin Chem Biol, 12,
565-572.
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A.G.Watts,
P.Oppezzo,
S.G.Withers,
P.M.Alzari,
and
A.Buschiazzo
(2006).
Structural and kinetic analysis of two covalent sialosyl-enzyme intermediates on Trypanosoma rangeli sialidase.
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J Biol Chem, 281,
4149-4155.
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PDB codes:
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D.Indurugalla,
J.N.Watson,
and
A.J.Bennet
(2006).
Natural sialoside analogues for the determination of enzymatic rate constants.
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Org Biomol Chem, 4,
4453-4459.
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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
