β-Glucuronidase

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Beta-glucuronidase
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For α-glucuronidase, see alpha-glucuronidase.
"GUSB" redirects here. For the airport with this IATA code, see Sambailo Airport.
β-Glucuronidase
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β-Glucuronidase
Chr. 7 q11.21
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β-Glucuronidases are members of the

carbohydrates.[2] Human β-glucuronidase is a type of glucuronidase (a member of glycosidase Family 2) that catalyzes hydrolysis of β-D-glucuronic acid residues from the non-reducing end of mucopolysaccharides (also referred to as glycosaminoglycans) such as heparan sulfate.[2][3][4] Human β-glucuronidase is located in the lysosome.[5] In the gut, brush border β-glucuronidase converts conjugated bilirubin to the unconjugated form for reabsorption. β-Glucuronidase is also present in breast milk, which contributes to neonatal jaundice. The protein is encoded by the GUSB gene in humans[6][7] and by the uidA gene in bacteria.[8]

Structure

Human β-glucuronidase is synthesized as an 80 kDa

C-terminal end to form a 78 kDa monomer.[9][10]
β-Glucuronidase exists as a 332 kDa
β-barrel known as a jelly roll barrel and a TIM barrel.[1]

Mechanism of catalysis

Human β-glucuronidase is

acidic residues, respectively, and that the tyrosine
residue Tyr504 is also involved in catalysis. In support of this hypothesis, experimental
peptides after hydrolysis of a substrate that enters a very stable intermediate stage, researchers have determined that Glu540 is the nucleophilic residue.[15]

Though the particular type of

bond vibration period). These lifetimes are too short to assign to a reaction intermediate. From this evidence, it appears that these reactions, while having an SN1 appearance due to the oxocarbenium ion characteristics of their transition states, must be qualitatively SN2 reactions.[2]

The specific activity of Tyr504 in the catalytic mechanism is unclear.[14] Through comparison to the structural data of the homologous enzyme xylanase, it has been suggested that Tyr504 of β-glucuronidase might stabilize the leaving nucleophile (Glu540) or modulate its activity.[16]

In addition to these residues, a conserved asparagine residue (Asn450) has been suggested to stabilize the substrate through the action of a hydrogen bond at the 2-hydroxyl group of the sugar substrate.[11][17]

  • Repeating unit of the heparan sulfate substrate of β-glucuronidase
    Repeating unit of the heparan sulfate
    substrate
    of β-glucuronidase
  • Surface depiction of active site pocket of β-glucuronidase with catalytic residues shown[1]
    Surface depiction of active site pocket of β-glucuronidase with catalytic residues shown[1]
  • Mechanism of β-glucuronidase hydrolysis of a sugar substrate with high energy transition states showing oxocarbenium ion character depicted[15]
    Mechanism of β-glucuronidase hydrolysis of a sugar substrate with high energy transition states showing oxocarbenium ion character depicted[15]
  • Potential stabilization of the nucleophilic residue Glu540 by Tyr504 in β-glucuronidase[16]
    Potential stabilization of the nucleophilic residue Glu540 by Tyr504 in β-glucuronidase[16]
  • Predicted activity of the conserved Asn450 residue in stabilization of the β-glucuronidase sugar substrate[11][17]
    Predicted activity of the conserved Asn450 residue in stabilization of the β-glucuronidase sugar substrate[11][17]
  • Potential salt bridge between Glu352 and Arg216 in human beta-glucuronidase[1][18]
    Potential salt bridge between Glu352 and Arg216 in human beta-glucuronidase[1][18]

Sly syndrome

Main article: Sly syndrome

Deficiencies in β-glucuronidase result in the

salt bridge with Glu352; therefore, Glu352 is likely involved in stabilizing the interaction between two different three-dimensional domains of the enzyme.[1]

Use as a reporter gene

In

GUS assay allows determination of the spatial and temporal expression of the gene in question.[21]

See also

References

  1. ^
    S2CID 28862883
    .
  2. ^
    ISBN 978-0-12-646864-9
    .
  3. PMID 7712292
    .
  4. doi:10.1021/cr00105a006
    .
  5. ^
    ISBN 978-0-340-80970-9
    .
  6. PMID 3468507
    .
  7. ^ "Entrez Gene: GUSB glucuronidase, beta".
  8. PMID 8357258
    .
  9. PMID 8226771
    .
  10. PMID 8505339
    .
  11. ^
    PMID 19052378
    .
  12. PMID 8352747
    .
  13. PMID 1747104
    .
  14. ^
    PMID 10438523
    .
  15. ^
    PMID 9852062
    .
  16. ^ a b "EzCatDB: T00066". EzCatDB: A Database of Catalytic Mechanisms. Archived from the original on 2009-06-17. Retrieved 2008-12-12.
  17. ^
    PMID 7624375
    .
  18. ^
    PMID 10366443
    .
  19. PMID 2495302
    .
  20. PMID 6436780
    .
  21. PMID 7867935
    .
  22. S2CID 8747218
    .

Further reading

External links
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