PDBsum entry 1fcu

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protein links
Hydrolase PDB id
Protein chain
324 a.a. *
Waters ×203
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure (trigonal) of bee venom hyaluronidase
Structure: Hyaluronoglucosaminidase. Chain: a. Synonym: hyaluronidase, api m ii. Engineered: yes
Source: Apis mellifera. Honey bee. Organism_taxid: 7460. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell: high-five insect cells.
2.10Å     R-factor:   0.209     R-free:   0.257
Authors: Z.Markovic-Housley,G.Miglierini,L.Soldatova,P.J.Rizkallah, U.Mueller,T.Schirmer
Key ref:
Z.Marković-Housley et al. (2000). Crystal structure of hyaluronidase, a major allergen of bee venom. Structure, 8, 1025-1035. PubMed id: 11080624 DOI: 10.1016/S0969-2126(00)00511-6
19-Jul-00     Release date:   01-Oct-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q08169  (HUGA_APIME) -  Hyaluronidase
382 a.a.
324 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Hyaluronoglucosaminidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Random hydrolysis of 1->4-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     metabolic process   3 terms 
  Biochemical function     catalytic activity     4 terms  


DOI no: 10.1016/S0969-2126(00)00511-6 Structure 8:1025-1035 (2000)
PubMed id: 11080624  
Crystal structure of hyaluronidase, a major allergen of bee venom.
Z.Marković-Housley, G.Miglierini, L.Soldatova, P.J.Rizkallah, U.Müller, T.Schirmer.
BACKGROUND: Hyaluronic acid (HA) is the most abundant glycosaminoglycan of vertebrate extracellular spaces and is specifically degraded by a beta-1,4 glycosidase. Bee venom hyaluronidase (Hya) shares 30% sequence identity with human hyaluronidases, which are involved in fertilization and the turnover of HA. On the basis of sequence similarity, mammalian enzymes and Hya are assigned to glycosidase family 56 for which no structure has been reported yet. RESULTS: The crystal structure of recombinant (Baculovirus) Hya was determined at 1.6 A resolution. The overall topology resembles a classical (beta/alpha)(8) TIM barrel except that the barrel is composed of only seven strands. A long substrate binding groove extends across the C-terminal end of the barrel. Cocrystallization with a substrate analog revealed the presence of a HA tetramer bound to subsites -4 to -1 and distortion of the -1 sugar. CONCLUSIONS: The structure of the complex strongly suggest an acid-base catalytic mechanism, in which Glu113 acts as the proton donor and the N-acetyl group of the substrate is the nucleophile. The location of the catalytic residues shows striking similarity to bacterial chitinase which also operates via a substrate-assisted mechanism.
  Selected figure(s)  
Figure 2.
Figure 2. Representative Section of the Final Electron Density MapClose-up stereo view of the segment 111-116, including the proton donor Glu113, overlaid onto the final SigmaA-weighted 2F[o]-F[c] map [71] contoured at 1s. Figure 2, Figure 3, Figure 5, Figure 6 and Figure 7 were produced using the program DINO (A. Philippsen,

  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 1025-1035) copyright 2000.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20608917 D.Ma, Y.Li, J.Dong, S.An, Y.Wang, C.Liu, X.Yang, H.Yang, X.Xu, D.Lin, and R.Lai (2011).
Purification and characterization of two new allergens from the salivary glands of the horsefly, Tabanus yao.
  Allergy, 66, 101-109.  
20553495 I.Magler, D.Nüss, M.Hauser, F.Ferreira, and H.Brandstetter (2010).
Molecular metamorphosis in polcalcin allergens by EF-hand rearrangements and domain swapping.
  FEBS J, 277, 2598-2610.  
20140203 J.Rouvinen, J.Jänis, M.L.Laukkanen, S.Jylhä, M.Niemi, T.Päivinen, S.Mäkinen-Kiljunen, T.Haahtela, H.Söderlund, and K.Takkinen (2010).
Transient dimers of allergens.
  PLoS One, 5, e9037.  
20396401 T.M.Gloster, and D.J.Vocadlo (2010).
Mechanism, Structure, and Inhibition of O-GlcNAc Processing Enzymes.
  Curr Signal Transduct Ther, 5, 74-91.  
20066263 T.M.Gloster, and G.J.Davies (2010).
Glycosidase inhibition: assessing mimicry of the transition state.
  Org Biomol Chem, 8, 305-320.  
20552664 T.V.Vuong, and D.B.Wilson (2010).
Glycoside hydrolases: catalytic base/nucleophile diversity.
  Biotechnol Bioeng, 107, 195-205.  
19181667 D.W.Abbott, M.S.Macauley, D.J.Vocadlo, and A.B.Boraston (2009).
Streptococcus pneumoniae Endohexosaminidase D, Structural and Mechanistic Insight into Substrate-assisted Catalysis in Family 85 Glycoside Hydrolases.
  J Biol Chem, 284, 11676-11689.
PDB codes: 2w91 2w92
19479740 J.H.Baek, T.H.Woo, C.B.Kim, J.H.Park, H.Kim, S.Lee, and S.H.Lee (2009).
Differential gene expression profiles in the venom gland/sac of Orancistrocerus drewseni (Hymenoptera: Eumenidae).
  Arch Insect Biochem Physiol, 71, 205-222.  
19201751 L.Zhang, A.G.Bharadwaj, A.Casper, J.Barkley, J.J.Barycki, and M.A.Simpson (2009).
Hyaluronidase activity of human Hyal1 requires active site acidic and tyrosine residues.
  J Biol Chem, 284, 9433-9442.  
19478093 S.Reitinger, J.Müllegger, B.Greiderer, J.E.Nielsen, and G.Lepperdinger (2009).
Designed Human Serum Hyaluronidase 1 Variant, HYAL1{Delta}L, Exhibits Activity up to pH 5.9.
  J Biol Chem, 284, 19173-19177.  
18344557 D.C.Martin, V.Atmuri, R.J.Hemming, J.Farley, J.S.Mort, S.Byers, S.Hombach-Klonisch, A.B.Csoka, R.Stern, and B.L.Triggs-Raine (2008).
A mouse model of human mucopolysaccharidosis IX exhibits osteoarthritis.
  Hum Mol Genet, 17, 1904-1915.  
17620008 E.S.Hofinger, J.Hoechstetter, M.Oettl, G.Bernhardt, and A.Buschauer (2008).
Isoenzyme-specific differences in the degradation of hyaluronic acid by mammalian-type hyaluronidases.
  Glycoconj J, 25, 101-109.  
18508614 M.A.Simpson, and V.B.Lokeshwar (2008).
Hyaluronan and hyaluronidase in genitourinary tumors.
  Front Biosci, 13, 5664-5680.  
18448355 V.B.Lokeshwar, and M.G.Selzer (2008).
Hyalurondiase: both a tumor promoter and suppressor.
  Semin Cancer Biol, 18, 281-287.  
18820742 V.Volfova, J.Hostomska, M.Cerny, J.Votypka, and P.Volf (2008).
Hyaluronidase of bloodsucking insects and its enhancing effect on leishmania infection in mice.
  PLoS Negl Trop Dis, 2, e294.  
18265954 W.Hemmer (2008).
[Cross-reactivity to honeybee and wasp venom]
  Hautarzt, 59, 194-199.  
17443842 D.Kolarich, A.Loos, R.Léonard, L.Mach, G.Marzban, W.Hemmer, and F.Altmann (2007).
A proteomic study of the major allergens from yellow jacket venoms.
  Proteomics, 7, 1615-1623.  
17439950 K.A.Stubbs, M.Balcewich, B.L.Mark, and D.J.Vocadlo (2007).
Small molecule inhibitors of a glycoside hydrolase attenuate inducible AmpC-mediated beta-lactam resistance.
  J Biol Chem, 282, 21382-21391.
PDB code: 2oxn
17502382 K.E.van Straaten, T.R.Barends, B.W.Dijkstra, and A.M.Thunnissen (2007).
Structure of Escherichia coli Lytic transglycosylase MltA with bound chitohexaose: implications for peptidoglycan binding and cleavage.
  J Biol Chem, 282, 21197-21205.
PDB codes: 2pi8 2pic 2pjj
17705309 M.Ohmae, K.Sakaguchi, T.Kaneto, S.Fujikawa, and S.Kobayashi (2007).
Keratanase II-catalyzed synthesis of keratan sulfate oligomers by using sugar oxazolines as transition-state analogue substrate monomers: a novel insight into the enzymatic catalysis mechanism.
  Chembiochem, 8, 1710-1720.  
17293874 S.Banerji, A.J.Wright, M.Noble, D.J.Mahoney, I.D.Campbell, A.J.Day, and D.G.Jackson (2007).
Structures of the Cd44-hyaluronan complex provide insight into a fundamental carbohydrate-protein interaction.
  Nat Struct Mol Biol, 14, 234-239.
PDB codes: 2jcp 2jcq 2jcr
16510973 A.Dickmanns, M.Ballschmiter, W.Liebl, and R.Ficner (2006).
Structure of the novel alpha-amylase AmyC from Thermotoga maritima.
  Acta Crystallogr D Biol Crystallogr, 62, 262-270.
PDB code: 2b5d
16541109 F.V.Rao, H.C.Dorfmueller, F.Villa, M.Allwood, I.M.Eggleston, and D.M.van Aalten (2006).
Structural insights into the mechanism and inhibition of eukaryotic O-GlcNAc hydrolysis.
  EMBO J, 25, 1569-1578.
PDB codes: 2cbi 2cbj
16245359 K.Kemparaju, and K.S.Girish (2006).
Snake venom hyaluronidase: a therapeutic target.
  Cell Biochem Funct, 24, 7.  
16699186 L.K.Skov, U.Seppälä, J.J.Coen, N.Crickmore, T.P.King, R.Monsalve, J.S.Kastrup, M.D.Spangfort, and M.Gajhede (2006).
Structure of recombinant Ves v 2 at 2.0 Angstrom resolution: structural analysis of an allergenic hyaluronidase from wasp venom.
  Acta Crystallogr D Biol Crystallogr, 62, 595-604.
PDB code: 2atm
16522010 R.Stern, and M.J.Jedrzejas (2006).
Hyaluronidases: their genomics, structures, and mechanisms of action.
  Chem Rev, 106, 818-839.  
16807948 S.Kobayashi, M.Ohmae, H.Ochiai, and S.Fujikawa (2006).
A hyaluronidase supercatalyst for the enzymatic polymerization to synthesize glycosaminoglycans.
  Chemistry, 12, 5962-5971.  
16197464 B.M.Biló, F.Rueff, H.Mosbech, F.Bonifazi, and J.N.Oude-Elberink (2005).
Diagnosis of Hymenoptera venom allergy.
  Allergy, 60, 1339-1349.  
15718240 C.D.Blundell, A.Almond, D.J.Mahoney, P.L.DeAngelis, I.D.Campbell, and A.J.Day (2005).
Towards a structure for a TSG-6.hyaluronan complex by modeling and NMR spectroscopy: insights into other members of the link module superfamily.
  J Biol Chem, 280, 18189-18201.  
16206231 F.Karamloo, P.Schmid-Grendelmeier, F.Kussebi, M.Akdis, M.Salagianni, B.R.von Beust, A.Reimers, J.Zumkehr, L.Soldatova, Z.Housley-Markovic, U.Müller, T.Kündig, D.M.Kemeny, M.D.Spangfort, K.Blaser, and C.A.Akdis (2005).
Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes.
  Eur J Immunol, 35, 3268-3276.  
  16191204 F.M.Duh, C.Dirks, M.I.Lerman, and A.D.Miller (2005).
Amino acid residues that are important for Hyal2 function as a receptor for jaagsiekte sheep retrovirus.
  Retrovirology, 2, 59.  
16104017 M.J.Jedrzejas, and R.Stern (2005).
Structures of vertebrate hyaluronidases and their unique enzymatic mechanism of hydrolysis.
  Proteins, 61, 227-238.  
15795231 M.S.Macauley, G.E.Whitworth, A.W.Debowski, D.Chin, and D.J.Vocadlo (2005).
O-GlcNAcase uses substrate-assisted catalysis: kinetic analysis and development of highly selective mechanism-inspired inhibitors.
  J Biol Chem, 280, 25313-25322.  
16292497 N.Pan, X.Cai, K.Tang, and G.Zou (2005).
Unfolding features of bovine testicular hyaluronidase studied by fluorescence spectroscopy and fourier transformed infrared spectroscopy.
  J Fluoresc, 15, 841-847.  
15596803 V.Vigdorovich, R.K.Strong, and A.D.Miller (2005).
Expression and characterization of a soluble, active form of the jaagsiekte sheep retrovirus receptor, Hyal2.
  J Virol, 79, 79-86.  
15322107 A.Botzki, D.J.Rigden, S.Braun, M.Nukui, S.Salmen, J.Hoechstetter, G.Bernhardt, S.Dove, M.J.Jedrzejas, and A.Buschauer (2004).
L-Ascorbic acid 6-hexadecanoate, a potent hyaluronidase inhibitor. X-ray structure and molecular modeling of enzyme-inhibitor complexes.
  J Biol Chem, 279, 45990-45997.
PDB code: 1w3y
12972412 C.D.Blundell, D.J.Mahoney, A.Almond, P.L.DeAngelis, J.D.Kahmann, P.Teriete, A.R.Pickford, I.D.Campbell, and A.J.Day (2003).
The link module from ovulation- and inflammation-associated protein TSG-6 changes conformation on hyaluronan binding.
  J Biol Chem, 278, 49261-49270.
PDB codes: 1o7b 1o7c
12446724 M.Nukui, K.B.Taylor, D.T.McPherson, M.K.Shigenaga, and M.J.Jedrzejas (2003).
The function of hydrophobic residues in the catalytic cleft of Streptococcus pneumoniae hyaluronate lyase. Kinetic characterization of mutant enzyme forms.
  J Biol Chem, 278, 3079-3088.
PDB codes: 1n7n 1n7o 1n7p 1n7q 1n7r
12413546 A.Vasella, G.J.Davies, and M.Böhm (2002).
Glycosidase mechanisms.
  Curr Opin Chem Biol, 6, 619-629.  
12171933 S.J.Williams, B.L.Mark, D.J.Vocadlo, M.N.James, and S.G.Withers (2002).
Aspartate 313 in the Streptomyces plicatus hexosaminidase plays a critical role in substrate-assisted catalysis by orienting the 2-acetamido group and stabilizing the transition state.
  J Biol Chem, 277, 40055-40065.
PDB codes: 1m01 1m03 1m04
12100296 U.R.Müller (2002).
Recombinant Hymenoptera venom allergens.
  Allergy, 57, 570-576.  
12084718 V.B.Lokeshwar, G.L.Schroeder, R.I.Carey, M.S.Soloway, and N.Iida (2002).
Regulation of hyaluronidase activity by alternative mRNA splicing.
  J Biol Chem, 277, 33654-33663.  
11746691 A.Henriksen, T.P.King, O.Mirza, R.I.Monsalve, K.Meno, H.Ipsen, J.N.Larsen, M.Gajhede, and M.D.Spangfort (2001).
Major venom allergen of yellow jackets, Ves v 5: structural characterization of a pathogenesis-related protein superfamily.
  Proteins, 45, 438-448.
PDB code: 1qnx
11785764 A.J.Day, and J.K.Sheehan (2001).
Hyaluronan: polysaccharide chaos to protein organisation.
  Curr Opin Struct Biol, 11, 617-622.  
11964740 A.Pomés, and M.D.Chapman (2001).
Can knowledge of the molecular structure of allergens improve immunotherapy?
  Curr Opin Allergy Clin Immunol, 1, 549-554.  
11785761 Y.Bourne, and B.Henrissat (2001).
Glycoside hydrolases and glycosyltransferases: families and functional modules.
  Curr Opin Struct Biol, 11, 593-600.  
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