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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1v0e

E.C. nameendo-alpha-sialidase
SpeciesBacteriophage k1f ()
E.C. Number (IntEnz) 3.2.1.129
CSA Homologues of 1v0e1v0f,
CSA Entries With UniProtID Q04830
CSA Entries With EC Number 3.2.1.129
PDBe Entry 1v0e
PDBSum Entry 1v0e
MACiE Entry 1v0e

Literature Report

IntroductionE. coli K1, a major cause of neonatal sepsis and meningitis, surrounds itself in a capsule of poly alpha2,8-sialic acid (polySia), a sugar polymer that also acts as an important modulator of neuronal plasticity in the adult human host; hence, the mammalian immune system does not attack the bacterium.
The bacteriophage K1F can hydrolyse this bacterial capsule using an endosialidase, which is a mushroom-shaped homotrimer. This enzyme may find use in the diagnosis or therapy of polySia-bearing tumours, and in the treatment of meningitis caused by polySia-encapsulated bacteria.
MechansimEndosialidases are proposed to work by catalysing the intramolecular self-cleavage of polySia that occurs spontaneously in mild acidic conditions:
Arg 596 and Arg 647 bind the carboxyl group of polySia. This raises the pKa of the carboxyl so that it is protonated. The binding may also force the pyranose ring into an unfavourable boat conformation.
The proton is transferred (intramolecularly) between the carboxyl and the oxygen atom in the glycosidic linkage, making the linking oxygen a good leaving group.
The lone pair on the ring oxygen forms a -C=O+- bond, triggering the cleavage of the glycosidic bond and creating a planar, cationic transition state and intermediate that is stabilised by Glu 581.
Water is nucleophilic and attacks the carbon of the -C=O+- group, quenching the positive charge on oxygen and relieving the strained planar conformation of the intermediate.
The products formed have terminal sialic acid units, one a hemiacetal and the other a primary alcohol.
Reaction

Catalytic Sites for 1v0e

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA581581macie:sideChainStabilises the planar cationic transition states and intermediate.
ArgA596596macie:sideChainArg 596 increases the pKa of the carboxylate group of the substrate and effects the change of pyranose conformation.
ArgA647647macie:sideChainArg 647 increases the pKa of the carboxylate group of the substrate and effects the change of pyranose conformation.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluB581581macie:sideChainStabilises the planar cationic transition states and intermediate.
ArgB596596macie:sideChainArg 596 increases the pKa of the carboxylate group of the substrate and effects the change of pyranose conformation.
ArgB647647macie:sideChainArg 647 increases the pKa of the carboxylate group of the substrate and effects the change of pyranose conformation.

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluC581581macie:sideChainStabilises the planar cationic transition states and intermediate.
ArgC596596macie:sideChainArg 596 increases the pKa of the carboxylate group of the substrate and effects the change of pyranose conformation.
ArgC647647macie:sideChainArg 647 increases the pKa of the carboxylate group of the substrate and effects the change of pyranose conformation.

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluD581581macie:sideChainStabilises the planar cationic transition states and intermediate.
ArgD596596macie:sideChainArg 596 increases the pKa of the carboxylate group of the substrate and effects the change of pyranose conformation.
ArgD647647macie:sideChainArg 647 increases the pKa of the carboxylate group of the substrate and effects the change of pyranose conformation.

Annotated By Reference To The Literature - Site 5 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluE581581macie:sideChainStabilises the planar cationic transition states and intermediate.
ArgE596596macie:sideChainArg 596 increases the pKa of the carboxylate group of the substrate and effects the change of pyranose conformation.
ArgE647647macie:sideChainArg 647 increases the pKa of the carboxylate group of the substrate and effects the change of pyranose conformation.

Annotated By Reference To The Literature - Site 6 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluF581581macie:sideChainStabilises the planar cationic transition states and intermediate.
ArgF596596macie:sideChainArg 596 increases the pKa of the carboxylate group of the substrate and effects the change of pyranose conformation.
ArgF647647macie:sideChainArg 647 increases the pKa of the carboxylate group of the substrate and effects the change of pyranose conformation.

Literature References

Notes:
Stummeyer K
Crystal structure of the polysialic acid-degrading endosialidase of bacteriophage K1F.
Nat Struct Mol Biol 2005 12 90-96
PubMed: 15608653
Manzi AE
Intramolecular self-cleavage of polysialic acid.
J Biol Chem 1994 269 23617-23624
PubMed: 8089131
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