EzCatDB: D00804
Related links:    PDB-formatted query search system Fasta-formatted query search system Fasta-formatted query search system

DB codeD00804
RLCP classification1.32.68230.73 : Hydrolysis
CATH domainDomain 13.20.20.70 : TIM BarrelCatalytic domain
Domain 22.-.-.-
E.C.3.2.1.35

CATH domainRelated DB codes (homologues)
3.20.20.70 : TIM BarrelS00215,S00217,S00218,S00219,S00532,S00198,S00220,S00745,S00537,S00538,S00539,S00826,S00841,S00235,S00239,S00240,S00243,S00244,S00199,S00200,S00201,S00221,S00222,S00847,S00224,S00225,S00226,D00014,D00029,M00141,T00015,T00239,D00664,D00665,D00863,T00089

Enzyme Name
UniProtKBKEGG

Q12794
Protein nameHyaluronidase-1Hyaluronoglucosaminidase
Hyaluronidase
Hyaluronoglucosidase
Chondroitinase
Chondroitinase I
SynonymsHyal-1
EC 3.2.1.35
Hyaluronoglucosaminidase-1
Lung carcinoma protein 1
LuCa-1
RefSeqNP_149349.2 (Protein)
NM_033159.3 (DNA/RNA sequence)
NP_695013.1 (Protein)
NM_153281.1 (DNA/RNA sequence)
NP_695014.1 (Protein)
NM_153282.2 (DNA/RNA sequence)
NP_695015.1 (Protein)
NM_153283.2 (DNA/RNA sequence)
NP_695017.1 (Protein)
NM_153285.2 (DNA/RNA sequence)
PfamPF01630 (Glyco_hydro_56)
[Graphical view]
CAZyGH56 (Glycoside Hydrolase Family)

KEGG pathways
MAP codePathways
MAP00531Glycosaminoglycan degradation
MAP01032Glycan structures - degradation

UniProtKB:Accession NumberQ12794
Entry nameHYAL1_HUMAN
ActivityRandom hydrolysis of 1->4-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate.
Subunit
Subcellular locationSecreted. Lysosome.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00518C00401C00634C00635C00001C00518C00401C00634C00635I00111
CompoundHyaluronateChondroitinChondroitin 4-sulfateChondroitin 6-sulfateH2OHyaluronateChondroitinChondroitin 4-sulfateChondroitin 6-sulfateIntramolecular cyclic intermediate at reducing end of hyaluronate
Typeamide group,carboxyl group,polysaccharideamide group,carbohydrate,carboxyl group,polysaccharideamide group,carbohydrate,carboxyl group,polysaccharide,sulfate groupamide group,carbohydrate,carboxyl group,polysaccharide,sulfate groupH2Oamide group,carboxyl group,polysaccharideamide group,carbohydrate,carboxyl group,polysaccharideamide group,carbohydrate,carboxyl group,polysaccharide,sulfate groupamide group,carbohydrate,carboxyl group,polysaccharide,sulfate group
ChEBI



15377





PubChem



962
22247451





                  
2pe4A01UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound
2pe4A02UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [8], [9]
pdbCatalytic residues
         
2pe4A01ASP 129;GLU 131;TYR 247
2pe4A02 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]Fig.1 p.7955
[7]Fig.6, p. 234-235
[8]Fig.6 p.832-833
[9]p.6914

references
[1]
PubMed ID8687420
JournalBiochem J
Year1996
Volume316
Pages695-6
AuthorsHenrissat B, Bairoch A
TitleUpdating the sequence-based classification of glycosyl hydrolases.
[2]
PubMed ID9288901
JournalEur J Biochem
Year1997
Volume247
Pages810-4
AuthorsArming S, Strobl B, Wechselberger C, Kreil G
TitleIn vitro mutagenesis of PH-20 hyaluronidase from human sperm.
[3]
JournalJ Am Chem Soc
Year1997
Volume119
Pages7954-59
AuthorsTews I, vanScheltinga ACT, Perrakis A, Wilson KS, Dijkstra BW
TitleSubstrate-Assisted Catalysis Unifies Two Families of Chitinolytic Enzymes
[4]
CommentsX-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 42-362, AND ACTIVE SITE.
PubMed ID11080624
JournalStructure
Year2000
Volume8
Pages1025-35
AuthorsMarkovic-Housley Z, Miglierini G, Soldatova L, Rizkallah PJ, Muller U, Schirmer T
TitleCrystal structure of hyaluronidase, a major allergen of bee venom.
Related PDB1fcq,1fcu,1fcv
Related UniProtKBQ08169
[5]
PubMed ID10907797
JournalCrit Rev Biochem Mol Biol
Year2000
Volume35
Pages221-51
AuthorsJedrzejas MJ
TitleStructural and functional comparison of polysaccharide-degrading enzymes.
[6]
PubMed ID11731267
JournalMatrix Biol
Year2001
Volume20
Pages499-508
AuthorsCsoka AB, Frost GI, Stern R
TitleThe six hyaluronidase-like genes in the human and mouse genomes.
[7]
PubMed ID16104017
JournalProteins
Year2005
Volume61
Pages227-38
AuthorsJedrzejas MJ, Stern R
TitleStructures of vertebrate hyaluronidases and their unique enzymatic mechanism of hydrolysis.
[8]
PubMed ID16522010
JournalChem Rev
Year2006
Volume106
Pages818-39
AuthorsStern R, Jedrzejas MJ
TitleHyaluronidases: their genomics, structures, and mechanisms of action.
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 20-435; MASS SPECTROMETRY, GLYCOSYLATION AT ASN-99; ASN-216 AND ASN-350, AND DISULFIDE BONDS.
PubMed ID17503783
JournalBiochemistry
Year2007
Volume46
Pages6911-20
AuthorsChao KL, Muthukumar L, Herzberg O
TitleStructure of human hyaluronidase-1, a hyaluronan hydrolyzing enzyme involved in tumor growth and angiogenesis.
Related PDB2pe4
Related UniProtKBQ12794
[10]
PubMed ID17602139
JournalGlycobiology
Year2007
Volume17
Pages963-71
AuthorsHofinger ES, Bernhardt G, Buschauer A
TitleKinetics of Hyal-1 and PH-20 hyaluronidases: comparison of minimal substrates and analysis of the transglycosylation reaction.
[11]
PubMed ID17408700
JournalLife Sci
Year2007
Volume80
Pages1921-43
AuthorsGirish KS, Kemparaju K
TitleThe magic glue hyaluronan and its eraser hyaluronidase: a biological overview.
[12]
PubMed ID17620008
JournalGlycoconj J
Year2008
Volume25
Pages101-9
AuthorsHofinger ES, Hoechstetter J, Oettl M, Bernhardt G, Buschauer A
TitleIsoenzyme-specific differences in the degradation of hyaluronic acid by mammalian-type hyaluronidases.

comments
This enzyme belongs to the glycosidase family-56 with a retaining mechanism.
According to the literature [5], this enzyme hydrolyzes beta-N-acetyl-hexosamine-(1->4) glycosidic bonds in chondroitin and chondroitin-suflate as well as in hyarulonan.
According to the literature [4], [7], [8] and [9], this enzyme catalyzes the following reaction:
(0) Asp 129 may modulate the pKa of Glu131. On the other hand, the nucleophile, N-acetyl group of substrate can be modulated by Asp129 and Tyr247 (see [4]). Moreover, the interaction of the nucleophilic N-acetyl group with these residues may induce the deformation of the sugar ring from chair to distorted boat conformation, which facilitate the formation of oxocarbonium ion transtion-state (SN1-like reaction).
(1) The carbonyl oxygen of the N-acetyl group makes a nucleophilic attack on the C1 atom of the same sugar unit, to form an intramolecular covalent intermediate. At the same time, Glu131 acts as a general acid to protonate the leaving glycan on the reducing side of the glycosidic bond to be cleaved. Thus, the glycosidic bond in the substrate on the non-reducing side of the bond is cleaved, resulting in the inversion of the anomeric C1 atom configuration.
(2) Glu131 acts as a general base to activate a water molecule.
(3) The activated water makes a nucleophilic attack on the C1 atom of the intermediate, resulting in the second inversion of the C1 configuration. Thus, the reaction completes.

createdupdated
2008-07-282011-12-22


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
© Biotechnology Research Institute for Drug Discovery, AIST, 2015-2016 All Rights Reserved.
© Computational Biology Research Center, AIST, 2004-2016 All Rights Reserved.