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8  structures 22  species 1  interaction 54  sequences 2  architectures

Family: Hyaluronidase_1 (PF07212)

Summary: Hyaluronidase protein (HylP)

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This is the Wikipedia entry entitled "Hyaluronidase". More...

Hyaluronidase Edit Wikipedia article

hyaluronoglucosaminidase
Hyaluronidase-1OJN.png
Identifiers
EC number 3.2.1.35
CAS number 37326-33-3
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
Hyaluronidase protein (HylP)
Identifiers
Symbol Hyaluronidase_1
Pfam PF07212
InterPro IPR009860
Hyaluronidase
Identifiers
Symbol Hyaluronidase_2
Pfam PF07555
InterPro IPR011496

The hyaluronidases (EC 3.2.1.35) are a family of enzymes that degrade hyaluronic acid.

In humans, there are six associated genes, including HYAL1, HYAL2, HYAL3, and PH-20/SPAM1.[1]

Use as a drug

Hyaluronidase
Systematic (IUPAC) name
hyaluronidase
Clinical data
AHFS/Drugs.com Consumer Drug Information
Pregnancy cat.
  • C
Legal status
?
Routes subcutaneous
Identifiers
CAS number 488712-31-8 YesY
ATC code B06AA03
DrugBank DB00070
UNII 8KOG53Z5EM YesY
ChEMBL CHEMBL1201636 N
Chemical data
Formula C2455H3775N617O704S21 
Mol. mass 53870.9 g/mol
 N (what is this?)  (verify)

By catalyzing the hydrolysis of hyaluronan, a constituent of the extracellular matrix (ECM), hyaluronidase lowers the viscosity of hyaluronan, thereby increasing tissue permeability. It is, therefore, used in medicine in conjunction with other drugs to speed their dispersion and delivery. Common applications are ophthalmic surgery, in combination with local anesthetics. It also increases the absorption rate of parenteral fluids given by hypodermoclysis, and is an adjunct in subcutaneous urography for improving resorption of radiopaque agents. Hyaluronidase is also used for extravasation of hyperosmolar solutions.

Brand names of animal-derived hyaluronidase include HydaseTM (developed and manufactured by PrimaPharm Inc., distributed by Akorn Inc.), which has been FDA-approved as a "thimerosal-free" animal-derived hyaluronidase, Vitrase (ISTA Pharmaceuticals), Amphadase (Amphastar Pharmaceuticals), and Wydase. Wydase, however, is no longer manufactured.

On December 2, 2005, the FDA approved a synthetic (recombinant or rDNA) "human" hyaluronidase, Hylenex (Halozyme Therapeutics).[2]abcd

Role in cancer

The role of hyaluronidases in cancer is controversial. Limited data support a role of lysosomal hyaluronidases in metastasis, while other data support a role in tumor suppression. Other studies suggest no contribution or effects independent of enzyme activity. Non-specific inhibitors (apigenin, sulfated glycosaminoglycans) or crude enzyme extracts have been used to test most hypotheses, making data difficult to interpret. It has been hypothesized that, by helping degrade the ECM surrounding the tumor, hyaluronidases help cancer cells escape from primary tumor masses. However, studies show that removal of hyaluronan from tumors prevents tumor invasion. Hyaluronidases are also thought to play a role in the process of angiogenesis, although most hyaluronidase preparations are contaminated with large amounts of angiogeneic growth factors.[3] As previously mentioned, there are six hyaluronidase genes in the human genome, three of which can express active hyaluronidases (HYAL1, HYAL2 and PH20).

Role in pathogenesis

Some bacteria, such as Staphylococcus aureus, Streptococcus pyogenes,[4] and Clostridium perfringens,[5] produce hyaluronidase as a means of using hyaluronan as a carbon source. It is often speculated that Streptococcus and Staphylococcus pathogens use hyaluronidase as a virulence factor to destroy the polysaccharide that holds animal cells together, making it easier for the pathogen to spread through the tissues of the host organism, but no valid experimental data are available to support this hypothesis.

Role in fertilization

In most mammalian fertilization, hyaluronidase is released by the acrosome of the sperm cell after it has reached the oocyte, by digesting hyaluronan in the corona radiata, thus enabling conception. Gene-targeting studies show that hyaluronidases such as PH20 are not essential for fertilization, although exogenous hyaluronidases can disrupt the cumulus matrix.

The majority of mammalian ova are covered in a layer of granulosa cells intertwined in an ECM that contains a high concentration of hyaluronan. When a capacitated sperm reaches the ovum, it is able to penetrate this layer with the assistance of hyaluronidase enzymes present on the surface of the sperm. Once this occurs, the sperm is capable of binding with the zona pellucida, and the acrosome reaction can occur.[6]

References

  1. ^ Csoka AB, Frost GI, Stern R (December 2001). "The six hyaluronidase-like genes in the human and mouse genomes". Matrix biology : journal of the International Society for Matrix Biology 20 (8): 499–508. doi:10.1016/S0945-053X(01)00172-X. PMID 11731267. 
  2. ^ "Halozyme Therapeutics and Baxter Healthcare Corporation Announce FDA Approval of Hylenex". Retrieved 2008-11-07. [dead link]
  3. ^ <Int J Cancer. 2002 Feb 10;97(5):601-7>[1]
  4. ^ Starr CR, Engleberg NC (January 2006). "Role of hyaluronidase in subcutaneous spread and growth of group A streptococcus". Infection and immunity 74 (1): 40–8. doi:10.1128/IAI.74.1.40-48.2006. PMC 1346594. PMID 16368955. 
  5. ^ Zukaite V, Biziulevicius GA (March 2000). "Acceleration of hyaluronidase production in the course of batch cultivation of Clostridium perfringens can be achieved with bacteriolytic enzymes". Letters in applied microbiology 30 (3): 203–6. doi:10.1046/j.1472-765x.2000.00693.x. PMID 10747251. 
  6. ^ Alberts, Bruce (2008). Molecular biology of the cell. New York: Garland Science. p. 1298. ISBN 0-8153-4105-9. 

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Hyaluronidase protein (HylP) Provide feedback

This family consists of several phage associated hyaluronidase proteins ( EC:3.2.1.35) which seem to be specific to Streptococcus pyogenes and Streptococcus pyogenes bacteriophages. The substrate of hyaluronidase is hyaluronic acid, a sugar polymer composed of alternating N-acetylglucosamine and glucuronic acid residues. Hyaluronic acid is found in the ground substance of human connective tissue and the vitreous of the eye and also is the sole component of the capsule of group A streptococci. The capsule has been shown to be an important virulence factor of this organism by virtue of its ability to resist phagocytosis. Production by S. pyogenes of both a hyaluronic acid capsule and hyaluronidase enzymatic activity capable of destroying the capsule is an interesting, yet-unexplained, phenomenon [1].

Literature references

  1. Hynes WL, Hancock L, Ferretti JJ; , Infect Immun 1995;63:3015-3020.: Analysis of a second bacteriophage hyaluronidase gene from Streptococcus pyogenes: evidence for a third hyaluronidase involved in extracellular enzymatic activity. PUBMED:7622224 EPMC:7622224


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR009860

This family consists of several phage associated hyaluronidase proteins (EC) which seem to be specific to Streptococcus pyogenes and its bacteriophages. The substrate of hyaluronidase is hyaluronic acid, a sugar polymer composed of alternating N-acetylglucosamine and glucuronic acid residues. Hyaluronic acid is found in the ground substance of human connective tissue and the vitreous of the eye and also is the sole component of the capsule of group A streptococci. The capsule has been shown to be an important virulence factor of this organism by virtue of its ability to resist phagocytosis. Production by S. pyogenes of both a hyaluronic acid capsule and hyaluronidase enzymatic activity capable of destroying the capsule is an interesting, yet-unexplained, phenomenon [PUBMED:7622224].

Gene Ontology

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Domain organisation

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Meta
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RP35
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RP55
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RP75
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(52)
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RP15
(1)
RP35
(5)
RP55
(6)
RP75
(6)
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Curation and family details

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Curation View help on the curation process

Seed source: Pfam-B_16578 (release 10.0)
Previous IDs: Hyaluronidase;
Type: Family
Author: Moxon SJ
Number in seed: 2
Number in full: 54
Average length of the domain: 239.80 aa
Average identity of full alignment: 70 %
Average coverage of the sequence by the domain: 77.07 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 37.3 56.6
Noise cut-off 19.6 19.6
Model length: 277
Family (HMM) version: 6
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Interactions

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Hyaluronidase_1

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Hyaluronidase_1 domain has been found. There are 8 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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