EzCatDB: S00745
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DB codeS00745
RLCP classification1.32.68230.73 : Hydrolysis
CATH domainDomain 13.20.20.70 : TIM BarrelCatalytic domain
E.C.3.2.1.35
CSA1fcq

CATH domainRelated DB codes (homologues)
3.20.20.70 : TIM BarrelS00215,S00217,S00218,S00219,S00532,S00198,S00220,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,D00804,D00863,T00089

Enzyme Name
UniProtKBKEGG

P49370Q08169
Protein nameHyaluronidase A (Hya A) (EC 3.2.1.35) (Hyaluronoglucosaminidase A) (Allergen Ves v II)AltName: Allergen=Ves v 2a;Hyaluronidase (Hya) (EC 3.2.1.35) (Hyaluronoglucosaminidase) (Allergen Api m II)AltName: Allergen=Api m 2;Hyaluronoglucosaminidase
Hyaluronidase
Hyaluronoglucosidase
Chondroitinase
Chondroitinase I
SynonymsNoneNone
RefSeq
NP_001011619.1 (Protein)
NM_001011619.1 (DNA/RNA sequence)
PfamPF01630 (Glyco_hydro_56)
[Graphical view]
PF01630 (Glyco_hydro_56)
[Graphical view]
CAZyGH56 (Glycoside Hydrolase Family)
GH56 (Glycoside Hydrolase Family)

KEGG pathways
MAP codePathways
MAP00531Glycosaminoglycan degradation
MAP01032Glycan structures - degradation

UniProtKB:Accession NumberP49370Q08169
Entry nameHUGA_VESVUHUGA_APIME
ActivityRandom hydrolysis of 1->4-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate.Random hydrolysis of 1->4-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate.
Subunit
Homotetramer.
Subcellular locationSecreted.Secreted.@
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,carbohydrate,polysaccharideamide group,carbohydrate,carboxyl group,polysaccharideamide group,carbohydrate,carboxyl group,polysaccharide,sulfate groupamide group,carbohydrate,carboxyl group,polysaccharide,sulfate groupH2Oamide group,carbohydrate,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





                  
2atmA00UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1fcqA00UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1fcuA00UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1fcvA00UnboundUnboundUnboundUnbound Bound:GCU-NAG-GCU-NAG-GCUUnboundUnboundUnboundUnbound
2j88A00UnboundUnboundUnboundUnbound UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [5], [7]
pdbCatalytic residues
         
2atmA00ASP 107;GLU 109;TYR 223
1fcqA00ASP 111;GLU 113;TYR 227
1fcuA00ASP 111;GLU 113;TYR 227
1fcvA00ASP 111;GLU 113;TYR 227
2j88A00ASP 111;GLU 113;TYR 227

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]Fig.1, p. 7955
[5]Fig.3, Fig.6, Fig.7, p. 1029-1030
[6]Fig.6, p.235
[8]Fig.6, p. 832-833

references
[1]
PubMed ID8687420
JournalBiochem J
Year1996
Volume316
Pages695-6
AuthorsHenrissat B, Bairoch A
TitleUpdating the sequence-based classification of glycosyl hydrolases.
[2]
PubMed ID8952478
JournalBiochemistry
Year1996
Volume35
Pages15280-7
AuthorsSulzenbacher G, Driguez H, Henrissat B, Schulein M, Davies GJ
TitleStructure of the Fusarium oxysporum endoglucanase I with a nonhydrolyzable substrate analogue: substrate distortion gives rise to the preferred axial orientation for the leaving group.
[3]
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.
[4]
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
[5]
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
[6]
PubMed ID16104017
JournalProteins
Year2005
Volume61
Pages227-38
AuthorsJedrzejas MJ, Stern R
TitleStructures of vertebrate hyaluronidases and their unique enzymatic mechanism of hydrolysis.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-331, PARTIAL PROTEIN SEQUENCE, MASS SPECTROMETRY, GLYCOSYLATION AT ASN-79; ASN-99 AND ASN-127, AND DISULFIDE BONDS.
PubMed ID16699186
JournalActa Crystallogr D Biol Crystallogr
Year2006
Volume62
Pages595-604
AuthorsSkov LK, Seppala U, Coen JJ, Crickmore N, King TP, Monsalve R, Kastrup JS, Spangfort MD, Gajhede M
TitleStructure of recombinant Ves v 2 at 2.0 Angstrom resolution: structural analysis of an allergenic hyaluronidase from wasp venom.
Related PDB2atm
Related UniProtKBP49370
[8]
PubMed ID16522010
JournalChem Rev
Year2006
Volume106
Pages818-39
AuthorsStern R, Jedrzejas MJ
TitleHyaluronidases: their genomics, structures, and mechanisms of action.
[9]
CommentsX-RAY DIFFRACTION
PubMed ID17374540
JournalJ Mol Biol
Year2007
Volume368
Pages742-52
AuthorsPadavattan S, Schirmer T, Schmidt M, Akdis C, Valenta R, Mittermann I, Soldatova L, Slater J, Mueller U, Markovic-Housley Z
TitleIdentification of a B-cell epitope of hyaluronidase, a major bee venom allergen, from its crystal structure in complex with a specific Fab.
Related PDB2j88
[10]
PubMed ID17408700
JournalLife Sci
Year2007
Volume80
Pages1921-43
AuthorsGirish KS, Kemparaju K
TitleThe magic glue hyaluronan and its eraser hyaluronidase: a biological overview.

comments
This enzyme belongs to the glycosidase family-56 with a retaining mechanism.
This enzyme hydrolyzes beta-N-acetyl-hexosamine-(1->4) glycosidic bonds in chondroitin and chondroitin-suflate as well as in hyarulonan (see ref.[5] of D00804 in EzCatDB).
According to the literature [4], [5], [6] and [8], this enzyme catalyzes the following reaction:
(0) Asp 111 (of 1fcv) may modulate the pKa of Glu113. On the other hand, the nucleophile, N-acetyl group of substrate can be modulated by Asp111 and Tyr227 (see [5]). 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) Glu113 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
2008-07-292011-12-26


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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)
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